Examinando por Autor "D'Marco, Luis"
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Ítem Advanced Glycation End Products: New Clinical and Molecular Perspectives(MDPI, 2021) Salazar, Juan; Navarro, Carla; Ortega, Ángel; Nava, Manuel; Morillo, Daniela; Torres, Wheeler; Hernández, Marlon; Cabrera, Mayela; Angarita, Lissé; Ortiz, Rina; Chacín, Maricarmen; D'Marco, Luis; Bermúdez, ValmoreDiabetes mellitus (DM) is considered one of the most massive epidemics of the twenty-first century due to its high mortality rates caused mainly due to its complications; therefore, the early identification of such complications becomes a race against time to establish a prompt diagnosis. The research of complications of DM over the years has allowed the development of numerous alternatives for diagnosis. Among these emerge the quantification of advanced glycation end products (AGEs) given their increased levels due to chronic hyperglycemia, while also being related to the induction of different stress-associated cellular responses and proinflammatory mechanisms involved in the progression of chronic complications of DM. Additionally, the investigation for more valuable and safe techniques has led to developing a newer, noninvasive, and effective tool, termed skin fluorescence (SAF). Hence, this study aimed to establish an update about the molecular mechanisms induced by AGEs during the evolution of chronic complications of DM and describe the newer measurement techniques available, highlighting SAF as a possible tool to measure the risk of developing DM chronic complications.Ítem Age-specific waist circumference cutoff-points for abdominal obesity diagnosis: a personalized strategy for a large Venezuelan population(Springer, 2021) Bermudez, Valmore; Salazar, Juan; Martínez, María Sofía; Olivar, Luis Carlos; Nava, Manuel; Rojas, Milagros; Ortega, Ángel; Añez, Roberto; Toledo, Alexandra; Rojas, Joselyn; Chacín, Maricarmen; Rodríguez, Johel E.; D'Marco, Luis; Cano, ClímacoBackground Evidence shows that the ageing process is a determining factor in fat distribution, composition, and functionality. The goal of this research was to determine cut-off points for waist circumference according to age in the adult population from Maracaibo city, Venezuela. Methodology The Metabolic Syndrome Prevalence Study is a descriptive, cross-sectional study with multi-stage randomized sampling. In this post-hoc analysis 1902 individuals ≥18 years and from both sexes were evaluated. Waist circumference ROC curves were built for each age group and sex, using metabolic phenotypes for classification. Results 52.2% (n = 992) were women, and the mean age was 38.7 ± 2. Cut-off points obtained for the <30 years age group were: 91 cm for women (Sensitivity: 96,8%, Specificity: 97,7%) and 94 cm for men (Sensitivity:100%, Specificity: 99,2%); for 30–49 years: women 94 cm (Sensitivity: 93.7%, Specificity: 97.1%) and men 95 cm (Sensitivity: 97.3%, Specificity: 100%); for ≥50 years: women 94 cm (Sensitivity: 91.8%, Specificity: 86.7%) and men 101 cm (Sensitivity: 100%, Specificity: 100%) Conclusion The use of specific cut-off points according to age groups is proposed to determine abdominal obesity in Maracaibo city due to the underestimation seen in young people and the overestimation observed in older people when using a unique cut-off point.Ítem Insulin Withdrawal in Diabetic Kidney Disease: What Are We Waiting for?(MDPI, 2021) Morillas, Carlos; D'Marco, Luis; Puchadas, María Jesús; Solá-Izquierdo, Eva; Gorriz-Zambrano, Carmen; Bermúdez, Valmore; Gorriz, José LuisThe prevalence of type 2 diabetes mellitus worldwide stands at nearly 9.3% and it is estimated that 20–40% of these patients will develop diabetic kidney disease (DKD). DKD is the leading cause of chronic kidney disease (CKD), and these patients often present high morbidity and mortality rates, particularly in those patients with poorly controlled risk factors. Furthermore, many are overweight or obese, due primarily to insulin compensation resulting from insulin resistance. In the last decade, treatment with sodium–glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP1-RA) have been shown to be beneficial in renal and cardiovascular targets; however, in patients with CKD, the previous guidelines recommended the use of drugs such as repaglinide or dipeptidyl peptidase-4 inhibitors (DPP-4 inhibitors), plus insulin therapy. However, new guidelines have paved the way for new treatments, such as SGLT2i or GLP1-RA in patients with CKD. Currently, the new evidence supports the use of GLP1-RA in patients with an estimated glomerular filtration rate (eGFR) of up to 15 mL/min/1.73 m2 and an SGLT2i should be started with an eGFR > 60 mL/min/1.73 m2. Regarding those patients in advanced stages of CKD, the usual approach is to switch to insulin. Thus, the add-on of GLP1-RA and/or SGLT2i to insulin therapy can reduce the dose of insulin, or even allow for its withdrawal, as well as achieve a good glycaemic control with no weight gain and reduced risk of hypoglycaemia, with the added advantage of cardiorenal benefits.Ítem Intrinsic and environmental basis of aging: A narrative review(Elsevier Ltd., 2023) Navarro, Carla; Salazar, Juan; Díaz, María P.; Chacin, Maricarmen; Santeliz, Raquel; Vera, Ivana; D'Marco, Luis; Parra, Heliana; Bernal, Mary Carlota; Castro, Ana; Escalona, Daniel; García-Pacheco, Henry; Bermúdez, ValmoreLongevity has been a topic of interest since the beginnings of humanity, yet its aetiology and precise mechanisms remain to be elucidated. Aging is currently viewed as a physiological phenomenon characterized by the gradual degeneration of organic physiology and morphology due to the passage of time where both external and internal stimuli intervene. The influence of intrinsic factors, such as progressive telomere shortening, genome instability due to mutation buildup, the direct or indirect actions of age-related genes, and marked changes in epigenetic, metabolic, and mitochondrial patterns constitute a big part of its underlying endogenous mechanisms. On the other hand, several psychosocial and demographic factors, such as diet, physical activity, smoking, and drinking habits, may have an even more significant impact on shaping the aging process. Consequentially, implementing dietary and exercise patterns has been proposed as the most viable alternative strategy for attenuating the most typical degenerative aging changes, thus increasing the likelihood of prolonging lifespan and achieving successful aging.Ítem Is “Leptin Resistance” Another Key Resistance to Manage Type 2 Diabetes?(Bentham Science Publishers, 2020) Salazar, Juan; Chávez-Castillo, Mervin; Rojas, Joselyn; Ortega, Ángel; Nava, Manuel; Pérez, José; Rojas, Milagros; Espinoza, Cristobal; Chacín, Maricarmen; Herazo, Yaneth; Angarita, Lissé; Rojas, Diana Marcela; D'Marco, Luis; Bermúdez, ValmoreAlthough novel pharmacological options for the treatment of type 2 diabetes mellitus (DM2) have been observed to modulate the functionality of several key organs in glucose homeostasis, successful regulation of insulin resistance (IR), body weight management, and pharmacological treatment of obesity remain notable problems in endocrinology. Leptin may be a pivotal player in this scenario, as an adipokine which centrally regulates appetite and energy balance. In obesity, excessive caloric intake promotes a low-grade inflammatory response, which leads to dysregulations in lipid storage and adipokine secretion. In turn, these entail alterations in leptin sensitivity, leptin transport across the blood-brain barrier and defects in post-receptor signaling. Furthermore, hypothalamic inflammation and endoplasmic reticulum stress may increase the expression of molecules which may disrupt leptin signaling. Abundant evidence has linked obesity and leptin resistance, which may precede or occur simultaneously to IR and DM2. Thus, leptin sensitivity may be a potential early therapeutic target that demands further preclinical and clinical research. Modulators of insulin sensitivity have been tested in animal models and small clinical trials with promising results, especially in combination with agents such as amylin and GLP-1 analogs, in particular, due to their central activity in the hypothalamus.Ítem The Role of the α Cell in the Pathogenesis of Diabetes: A World beyond the Mirror(MDPI, 2021) Martínez, María Sofía; Manzano, Alexander; Olivar, Luis Carlos; Nava, Manuel; Salazar, Juan; D'Marco, Luis; Ortiz, Rina; Chacín, Maricarmen; Guerrero-Wyss, Marion; Cabrera de Bravo, Mayela; Cano, Clímaco; Bermúdez, Valmore; Angarita, LisseType 2 Diabetes Mellitus (T2DM) is one of the most prevalent chronic metabolic disorders, and insulin has been placed at the epicentre of its pathophysiological basis. However, the involvement of impaired alpha (α) cell function has been recognized as playing an essential role in several diseases, since hyperglucagonemia has been evidenced in both Type 1 and T2DM. This phenomenon has been attributed to intra-islet defects, like modifications in pancreatic α cell mass or dysfunction in glucagon’s secretion. Emerging evidence has shown that chronic hyperglycaemia provokes changes in the Langerhans’ islets cytoarchitecture, including α cell hyperplasia, pancreatic beta (β) cell dedifferentiation into glucagon-positive producing cells, and loss of paracrine and endocrine regulation due to β cell mass loss. Other abnormalities like α cell insulin resistance, sensor machinery dysfunction, or paradoxical ATP-sensitive potassium channels (KATP) opening have also been linked to glucagon hypersecretion. Recent clinical trials in phases 1 or 2 have shown new molecules with glucagon-antagonist properties with considerable effectiveness and acceptable safety profiles. Glucagon-like peptide-1 (GLP-1) agonists and Dipeptidyl Peptidase-4 inhibitors (DPP-4 inhibitors) have been shown to decrease glucagon secretion in T2DM, and their possible therapeutic role in T1DM means they are attractive as an insulin-adjuvant therapy.Ítem SGLT2i and GLP-1RA in Cardiometabolic and Renal Diseases: From Glycemic Control to Adipose Tissue Inflammation and Senescence(Hindawi, 2021) D'Marco, Luis; Morillo, Valery; Gorriz, José Luis; Suarez, María K.; Nava, Manuel; Ortega, Ángel; Parra, Heliana; Villasmil, Nelson; Rojas-Quintero, Joselyn; Bermúdez, ValmoreBackground. Over the last few years, the use of sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide 1 receptor agonists (GLP-1RA) has increased substantially in medical practice due to their documented benefits in cardiorenal and metabolic health. In this sense, and in addition to being used for glycemic control in diabetic patients, these drugs also have other favorable effects such as weight loss and lowering blood pressure, and more recently, they have been shown to have cardio and renoprotective effects with anti-inflammatory properties. Concerning the latter, the individual or associated use of these antihyperglycemic agents has been linked with a decrease in proinflammatory cytokines and with an improvement in the inflammatory profile in chronic endocrine-metabolic diseases. Hence, these drugs have been positioned as first-line therapy in the management of diabetes and its multiple comorbidities, such as obesity, which has been associated with persistent inflammatory states that induce dysfunction of the adipose tissue. Moreover, other frequent comorbidities in long-standing diabetic patients are chronic complications such as diabetic kidney disease, whose progression can be slowed by SGLT2i and/or GLP-1RA. The neuroendocrine and immunometabolism mechanisms underlying adipose tissue inflammation in individuals with diabetes and cardiometabolic and renal diseases are complex and not fully understood. Summary. This review intends to expose the probable molecular mechanisms and compile evidence of the synergistic or additive anti-inflammatory effects of SGLT2i and GLP-1RA and their potential impact on the management of patients with obesity and cardiorenal compromise.Ítem The Sick Adipose Tissue: New Insights Into Defective Signaling and Crosstalk With the Myocardium(Frontiers Media, 2021) Bermúdez, Valmore; Durán, Pablo; Rojas, Edward; Díaz, María P.; Rivas, José; Nava, Manuel; Chací, Maricarmen; Cabrera de Bravo, Mayela; Carrasquero, Rubén; Cano Ponce, Clímaco; Górriz, José Luis; D'Marco, LuisAdipose tissue (AT) biology is linked to cardiovascular health since obesity is associated with cardiovascular disease (CVD) and positively correlated with excessive visceral fat accumulation. AT signaling to myocardial cells through soluble factors known as adipokines, cardiokines, branched-chain amino acids and small molecules like microRNAs, undoubtedly influence myocardial cells and AT function via the endocrine-paracrine mechanisms of action. Unfortunately, abnormal total and visceral adiposity can alter this harmonious signaling network, resulting in tissue hypoxia and monocyte/macrophage adipose infiltration occurring alongside expanded intra-abdominal and epicardial fat depots seen in the human obese phenotype. These processes promote an abnormal adipocyte proteomic reprogramming, whereby these cells become a source of abnormal signals, affecting vascular and myocardial tissues, leading to meta-inflammation, atrial fibrillation, coronary artery disease, heart hypertrophy, heart failure and myocardial infarction. This review first discusses the pathophysiology and consequences of adipose tissue expansion, particularly their association with meta-inflammation and microbiota dysbiosis. We also explore the precise mechanisms involved in metabolic reprogramming in AT that represent plausible causative factors for CVD. Finally, we clarify how lifestyle changes could promote improvement in myocardiocyte function in the context of changes in AT proteomics and a better gut microbiome profile to develop effective, non-pharmacologic approaches to CVD.