Advanced Glycation End Products: New Clinical and Molecular Perspectives

Diabetes 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

Microbiota and Diabetes Mellitus: Role of Lipid Mediators

Diabetes Mellitus (DM) is an inflammatory clinical entity with different mechanisms involved in its physiopathology. Among these, the dysfunction of the gut microbiota stands out. Currently, it is understood that lipid products derived from the gut microbiota are capable of interacting with cells from the immune system and have an immunomodulatory effect. In the presence of dysbiosis, the concentration of lipopolysaccharides (LPS) increases, favoring damage to the intestinal barrier. Furthermore, a pro-inflammatory environment prevails, and a state of insulin resistance and hyperglycemia is present. Conversely, during eubiosis, the production of short-chain fatty acids (SCFA) is fundamental for the maintenance of the integrity of the intestinal barrier as well as for immunogenic tolerance and appetite/satiety perception, leading to a protective effect. Additionally, it has been demonstrated that alterations or dysregulation of the gut microbiota can be reversed by modifying the eating habits of the patients or with the administration of prebiotics, probiotics, and symbiotics. Similarly, different studies have demonstrated that drugs like Metformin are capable of modifying the composition of the gut microbiota, promoting changes in the biosynthesis of LPS, and the metabolism of SCFA

Metabolic Syndrome: Is It Time to Add the Central Nervous System?

Metabolic syndrome (MS) is a set of cardio-metabolic risk factors that includes central obesity, hyperglycemia, hypertension, and dyslipidemias. The syndrome affects 25% of adults worldwide. The definition of MS has evolved over the last 80 years, with various classification systems and criteria, whose limitations and benefits are currently the subject of some controversy. Likewise, hypotheses regarding the etiology of MS add more confusion from clinical and epidemiological points of view. The leading suggestion for the pathophysiology of MS is insulin resistance (IR). IR can affect multiple tissues and organs, from the classic “triumvirate” (myocyte, adipocyte, and hepatocyte) to possible effects on organs considered more recently, such as the central nervous system (CNS). Mild cognitive impairment (MCI) and Alzheimer’s disease (AD) may be clinical expressions of CNS involvement. However, the association between MCI and MS is not understood. The bidirectional relationship that seems to exist between these factors raises the questions of which phenomenon occurs first and whether MCI can be a precursor of MS. This review explores shared pathophysiological mechanisms between MCI and MS and establishes a hypothesis of a possible MCI role in the development of IR and the appearance of MS

Role of Endocrine-Disrupting Chemicals in the Pathogenesis of Non-Alcoholic Fatty Liver Disease: A Comprehensive Review

Non-alcoholic fatty liver disease (NAFLD) is considered the most common liver disorder, affecting around 25% of the population worldwide. It is a complex disease spectrum, closely linked with other conditions such as obesity, insulin resistance, type 2 diabetes mellitus, and metabolic syndrome, which may increase liver-related mortality. In light of this, numerous efforts have been carried out in recent years in order to clarify its pathogenesis and create new prevention strategies. Currently, the essential role of environmental pollutants in NAFLD development is recognized. Particularly, endocrine-disrupting chemicals (EDCs) have a notable influence. EDCs can be classified as natural (phytoestrogens, genistein, and coumestrol) or synthetic, and the latter ones can be further subdivided into industrial (dioxins, polychlorinated biphenyls, and alkylphenols), agricultural (pesticides, insecticides, herbicides, and fungicides), residential (phthalates, polybrominated biphenyls, and bisphenol A), and pharmaceutical (parabens). Several experimental models have proposed a mechanism involving this group of substances with the disruption of hepatic metabolism, which promotes NAFLD. These include an imbalance between lipid influx/efflux in the liver, mitochondrial dysfunction, liver inflammation, and epigenetic reprogramming. It can be concluded that exposure to EDCs might play a crucial role in NAFLD initiation and evolution. However, further investigations supporting these effects in humans are required

New Insights into Alleviating Diabetes Mellitus: Role of Gut Microbiota and a Nutrigenomic Approach

The scientific literature has shown that diet is able to modify the gut microbiota and contribute to obesity and diabetes development. This process—characterized by inflammation and gut barrier disruption—can affect the immune system and alter the adipogenesis and insulin resistance. This chapter describes the advances in nutrigenomics and Human Intestinal Microbiota (HIM) modification, and its relation with diabetes mellitus type two (DM2). In context where health and feeding are the main concerns of the human being, food innovation takes a special interest to people that look for a healthy diet or demand a functional aliments, such as nutraceutical. Some products derived from diet and interaction with HIM module the expression of many genes on the host, the so-called epigenome, with favorable effects. Novel functional fiber like low-glycemic oligosaccharides and sweeteners shows a potential prebiotic activity giving a new focus of nutritional guidelines for control and prevention of DM2. The use of prebiotics derived from functional fiber sources, such as fructo-oligosaccharides and beta-glucans as well as lignin and keffir, can contribute to the development of a healthy HIM by promoting the growth of specific bacteria, some of them associated with the prevention of obesity and diabetes

The Microbiome and the Epigenetics of Diabetes Mellitus

Gut microbiota (GM) in the epigenetic mechanisms of diabetes mellitus and the reprogramming of the cells is a novel and emerging concept. The purpose of this chapter is to describe the modification of the GM and its relation with DM2. The increased risk of this disease is associated with changes in the amount of Bacteroides/Clostridium in the Firmicutes/Bacteroidetes ratio of people having DM. A dysbiosis state associated generates low-grade inflammation with similar characteristics that occur under metabolic syndrome, whose pattern is recognized by Toll-like receptor that recognizes important patterns of immunity. The synthesis of butyrate generated by intestinal microorganisms inhibits the metabolic pathway of histone deacetylase, promoting cellular differentiation, proliferation, and insulin resistance. On the other hand, the direct relationship between the neuroendocrine system and the GM has been demonstrated through the production of serotonin by enterochromaffin cells, whose action could influence the etiopathogenic factors of DM2

Efecto del consumo de una fórmula con carbohidratos de liberación prolongada sobre la respuesta glicémica e insulina post-prandial en individuos sanos

Existen fórmulas enterales específicas para mejorar el control glicémico en diabéticos; con carbohidratos cuya respuesta glicémica sería de interés indagar. Se determinó el efecto del consumo de una fórmula con carbohidratos de liberación prolongada sobre la respuesta glicémica e insulina post-prandial en 21 sujetos sanos; (11 hombres y 10 mujeres) entre (17 y 25 años), quienes consumieron en 2 ocasiones la fórmula enteral polimérica para diabéticos y el alimento de referencia (pan blanco), en una cantidad de 50 g de carbohidratos disponibles. La glicemia fue medida a los 0, 15, 30,45, 60, 75, 90, 105 y 120 min y las concentraciones de insulina en ayuno y a los 120 min. El área bajo la curva de glicemia fue calculada resultando más baja para la fórmula 11718,20. ± 1112,38 que para el pan blanco 13269,18 ± 1351,05, (p<0,001). El índice glicémico (IG) resultó intermedio (63,33±5,22), y más bajo al compararlo con los rangos de IG publicados para el alimento de referencia(80-96). Se produjo una menor concentración de glicemia posterior al consumo de la fórmula; sin incrementos en los requerimientos de insulina, presumiendo un uso adecuado en diabéticos y una respuesta de saciedad más prolongada. Este efecto y la hemoglobina glicosilada deberían estudiarse tras el consumo en períodos prolongados en sujetos con diabetes.There are specific formulas of enteral nutrition to improve glycemic control in diabetic patients containing different types of carbohydrates which glycemic response should be investigated. The consumption effect of a formula with carbohydrates with extended release was determined on the glycemic response and postprandial insulin in 21 healthy individuals (11 men and 10 women) from 17 to 25 years old, who consumed in two different time the polymeric enteral formula for diabetics and the reference food (white bread) in a quantity of 50 g of available carbohydrates. The glycemia was measured at 0, 15, 30, 45, 60, 75, 90, 105 and 120 min and the insulin concentrations in fasting and within 120 min. The area in the glycemic curve was measured being the lowest the formula 11718.20. ± 1112.38 than in white bread 13269.18 ± 1351.05 (P<0.001). The glycemic index (GI) resulted to be intermediate (63.33±5.22) and lower when compared to the GI ranks published for the reference food (80-96). A lower concentration of glycemia occurred after the consumption of the formula, without increments in the insulin requirements; thus, assuming an adequate use in diabetic and a more extended feeling of fullness. This effect and the glycated hemoglobin should be studied after the extended consumption in people with diabetes

Noncaloric Sweeteners in Children: A Controversial Theme

Noncaloric sweeteners (NCS) are food additives used to provide sweetness without adding calories. Their consumption has become more widespread around the world in all age groups, including children. The aim of this study is to show the state of the art about the intake of noncaloric sweeteners in children, as well as their benefits and consumption risk. Scientific searchers were used (PUBMED, Scopus, and Scielo) to analyze articles that included keywords (noncaloric sweeteners/saccharin/cyclamate/acesulfame potassium/aspartame/sucralose/stevia/children) in English, Spanish, and Portuguese. Authors conclude that it is imperative that health professionals judiciously and individually evaluate the overall benefits and risks of NCS use in consumers before recommending their use. Different subgroups of the population incorporate products containing NCS in their diet with different objectives, which should be considered when recommending a diet plan for the consumer. In childhood, in earlier age groups, this type of additives should be used as a dietary alternative when other forms of prevention in obesity are not sufficient

Efecto del consumo de una fórmula con carbohidratos de liberación prolongada sobre la respuesta glicémica e insulina post-prandial en individuos sanos

Existen fórmulas enterales específicas para mejorar el control glicémico en diabéticos; con carbohidratos cuya respuesta glicémica sería de interés indagar. Se determinó el efecto del consumo de una fórmula con carbohidratos de liberación prolongada sobre la respuesta glicémica e insulina post-prandial en 21 sujetos sanos; (11 hombres y 10 mujeres) entre (17 y 25 años), quienes consumieron en 2 ocasiones la fórmula enteral polimérica para diabéticos y el alimento de referencia (pan blanco), en una cantidad de 50 g de carbohidratos disponibles. La glicemia fue medida a los 0, 15, 30,45, 60, 75, 90, 105 y 120 min y las concentraciones de insulina en ayuno y a los 120 min. El área bajo la curva de glicemia fue calculada resultando más baja para la fórmula 11718,20. ± 1112,38 que para el pan blanco 13269,18 ± 1351,05, (p<0,001). El índice glicémico (IG) resultó intermedio (63,33±5,22), y más bajo al compararlo con los rangos de IG publicados para el alimento de referencia(80-96). Se produjo una menor concentración de glicemia posterior al consumo de la fórmula; sin incrementos en los requerimientos de insulina, presumiendo un uso adecuado en diabéticos y una respuesta de saciedad más prolongada. Este efecto y la hemoglobina glicosilada deberían estudiarse tras el consumo en períodos prolongados en sujetos con diabetes