Vitamin D and endocrine disorders: routine laboratory diagnostic implications

: The role of vitamin D in calcium-phosphorus metabolism regulation is the most highlighted, nonetheless there is enormous literature on the extra-skeletal effects of vitamin D, and lately new insight into the role of vitamin D in endocrine disease mechanisms has seen light of day. The present narrative review gives an overview of the proposed roles of vitamin D in the etiology of Hashimoto's thyroiditis, Grave's disease, Addison's disease and primary hyperthyroidism. The implications as pertaining to the routine laboratory practice are readily applicable to this patient group as well, and do not pose any additional challenge

The complex combination of COVID-19 and diabetes: pleiotropic changes in glucose metabolism

PURPOSE: Angiotensin converting enzyme 2 (ACE2) is the door for SARS-CoV-2, expressed in critical metabolic tissues. So, it is rational that the new virus causes pleiotropic alterations in glucose metabolism, resulting in the complication of pre-existing diabetes's pathophysiology or creating new disease mechanisms. However, it seems that less attention has been paid to this issue. This review aimed to highlight the importance of long-term consequences and pleiotropic alterations in glucose metabolism following COVID-19 and emphasize the need for basic and clinical research in metabolism and endocrinology.RESULTS: SARS-CoV-2 shifts cellular metabolism from oxidative phosphorylation to glycolysis, which leads to a decrease in ATP generation. Together with metabolic imbalance, the impaired immune system elevates the susceptibility of patients with diabetes to this deadly virus. SARS-CoV-2-induced metabolic alterations in immune cells can result in hyper inflammation and a cytokine storm. Metabolic dysfunction may affect therapies against SARS-CoV-2 infection. The effective control of metabolic complications could prove useful therapeutic targets for combating COVID-19. It is also necessary to understand the long-term consequences that will affect patients with diabetes who survived COVID-19.CONCLUSIONS: Since the pathophysiology of COVID-19 is still mostly unknown, identifying the metabolic mechanisms contributing to its progression is essential to provide specific ways to prevent and improve this dangerous virus's detrimental effects. The findings show that the new virus may induce new-onset diabetes with uncertain metabolic and clinical features, supporting a potential role of COVID-19 in the development of diabetes

Obesogenic endocrine disruptors and obesity: myths and truths

Obesogenic endocrine disruptors, also known as obesogens, are chemicals potentially involved in weight gain by altering lipid homeostasis and promoting adipogenesis and lipid accumulation. They included compounds to which human population is exposed over daily life such as pesticides/herbicides, industrial and household products, plastics, detergents and personal care products. The window of life during which the exposure happens could lead to different effects. A critical window is during utero and/or neonatal period in which the obesogens could cause subtle changes in gene expression and tissue organization or blunt other levels of biological organization leading to increased susceptibility to diseases in the adulthood. Some of the reasons for this increased sensitivity include the lack of the protective mechanisms that are available in adult such as DNA repair mechanisms, a competent immune system, detoxifying enzymes, liver metabolism and the blood/brain barrier still not fully functional in the fetus or newborn. The mechanisms of action of obesogens lay on their ability to increase the number and/or the size of the adipocytes and to alter appetite, satiety and food preferences. The ability of obesogens to increase fat deposition results in an increased capacity for their own retention due to their lipophilic properties; thus prolonging the exposure and increasing the detrimental metabolic consequences

Obesity and breast cancer in premenopausal women: Current evidence and future perspectives

There is raising evidence reporting an increased incidence of breast cancer over the past decades. Every year approximately 1.4 million new cases of breast cancer are diagnosed worldwide, with a mortality rate of approximately 450,000/year. Out of these cases, 6.6% are diagnosed in premenopausal women with a median age at diagnosis of 40 years: in premenopausal women breast cancer seems to be more aggressive than in post-menopausal women. Obesity has been reported to increase the risk of developing breast cancer and to worsen the prognosis. This seems to be due to several obesity-related mechanisms. Insulin resistance that often occurs with obesity may results in compensatory hyperinsulinemia. Insulin cross-binds insulin-like growth factor-I receptors expressed on breast cells, resulting in proliferative stimuli on breast cancer cells. Besides, hyperinsulinemia up-regulates the growth hormone receptor (GHR) thus increasing GHR stimulation and resulting in an increased hepatic IGF-I synthesis. Moreover, insulin decreases the hepatic expression of binding proteins of IGF-I, such as insulin-like growth factor binding proteins (IGFBP)-1 and IGFBP-2, thus leading to high circulating and bioavailable free IGF-I. Additionally, obesity is associated to chronic low-grade inflammation that has been reported to be an additional stimulus for tumor growth. This review shows the current evidence regarding to the association of obesity and breast cancer in premenopausal state focusing on both human and basic studies; showing that the obesity is a risk factor for breast cancer also among premenopausal women, especially for the molecular subtype Triple Negative Breast Cancer

Recomendações nutricionais em cuidados paliativos para pacientes com doenças avançadas e no final da vida

Palliative care (PC) is based on a multidisciplinary approach to the patient and their family to prevent and alleviate the suffering of the patient, promoting and maintaining an optimal quality of life until death. Food plays a fundamental role in people’s lives. Beyond nutrition, the fact that dying people have anorexia as part of their symptoms is difficult to accept as it means admitting death. A multidisciplinary plan to nutrition is essential, adapting to the disease stage and always considering that the benefits must outweigh the possible adverse effects. As an integral part of PC, artificial nutrition and hydration (ANH) can increase survival and improve quality of life in selected patients based on their pathology. Therefore, nutritional support should be prescribed according to the patient’s disease stage, energy and protein requirements, analyzing tolerability, and above all, respecting the wishes of the patient, family or caregiver. It is essential to know the patient, family, or caregivers’ preferences and achieve efficient communication within the health team. By doing so, it is possible to reach a shared understanding of the goals of palliative treatment among all members involved. This narrative review aims to describe the general and specific nutritional recommendations in the advanced stage and at the end of life phase of some of the primary diseases in which PCs play a vital part in offering a complete treatment to these specific patientsLos cuidados paliativos (CP) se basan en un abordaje multidisciplinar del paciente y su familia para prevenir y aliviar el sufrimiento del paciente, al promover y mantener una óptima calidad de vida hasta la muerte. La alimentación desempeña un papel fundamental en la vida de las personas. Más allá de la nutrición, el hecho de que las personas moribundas tengan anorexia como parte de sus síntomas es difícil de aceptar, ya que significa admitir la muerte. Un plan multidisciplinar de nutrición es fundamental, que se adapte al estadio de la enfermedad, siempre considerando que los beneficios deben superar los posibles efectos adversos. Como parte integral de la CP, la nutrición e hidratación artificiales (NHA) pueden aumentar la supervivencia y mejorar la calidad de vida en pacientes seleccionados en función de su patología. Por tanto, el soporte nutricional debe prescribirse de acuerdo con el estadio de la enfermedad del paciente y los requerimientos energéticos y proteicos, analizando la tolerabilidad y, sobre todo, respetando los deseos del paciente, la familia y el cuidador. Es fundamental conocer sus preferencias y lograr una comunicación eficiente dentro del equipo de salud. Al hacerlo, es posible alcanzar un entendimiento compartido de los objetivos del tratamiento paliativo entre todos los miembros involucrados. Esta revisión narrativa tiene como objetivo describir las recomendaciones nutricionales generales y específicas en la etapa avanzada y al final de la vida de algunas de las enfermedades primarias en las que los CP desempeñan un papel vital para ofrecer un tratamiento completo a estos pacientes específicos.Palliative care (PC) is based on a multidisciplinary approach to the patient and their family to prevent and alleviate the suffering of the patient, promoting and maintaining an optimal quality of life until death. Food plays a fundamental role in people’s lives. Beyond nutrition, the fact that dying people have anorexia as part of their symptoms is difficult to accept as it means admitting death. A multidisciplinary plan to nutrition is essential, adapting to the disease stage and always considering that the benefits must outweigh the possible adverse effects. As an integral part of PC, artificial nutrition and hydration (ANH) can increase survival and improve quality of life in selected patients based on their pathology. Therefore, nutritional support should be prescribed according to the patient’s disease stage, energy and protein requirements, analyzing tolerability, and above all, respecting the wishes of the patient, family or caregiver. It is essential to know the patient, family, or caregivers’ preferences and achieve efficient communication within the health team. By doing so, it is possible to reach a shared understanding of the goals of palliative treatment among all members involved. This narrative review aims to describe the general and specific nutritional recommendations in the advanced stage and at the end of life phase of some of the primary diseases in which PCs play a vital part in offering a complete treatment to these specific patients

Sleep disturbances: one of the culprits of obesity-related cardiovascular risk?

Growing evidence suggested that Sleep Disorders (SD) could increase the risk of developing obesity and could contribute to worsen obesity-related cardiovascular risk. Further, obesity per se has been reported to blunt sleep homeostasis. This happens through several mechanisms. First of all, the excessive adipose tissue at neck and chest levels could represent a mechanical obstacle to breathe. Moreover, the visceral adipose tissue is known to release cytokines contributing to low-grade chronic inflammation that could impair the circadian rhythm. Also, nutrition plays an important role in sleep homeostasis. High fat and/or high carbohydrate diets are known to have a negative impact on both sleep quality and duration. In addition, obesity predisposes to a condition called "obstructive sleep apnea" that has a detrimental effect on sleep. SD could increase the risk and/or could contribute to worsen cardiovascular risk usually associated with obesity. The chronic low grade inflammation associated with obesity has been reported to increase the risk of developing hypertension, type 2 diabetes and dyslipidemia. In turn, improving quality of sleep has been reported to improve the management of these cardiovascular risk factors. Thus, the aim of this manuscript is to provide evidence on the association of obesity and SD and on how they could contribute to the risk of developing cardiovascular risk factors such as hypertension, dyslipidemia and type 2 diabetes in obesity

Gender-related issues in the pharmacology of new anti-obesity drugs

Four new medicines-liraglutide, lorcaserin, bupropion/naltrexone, and phentermine/topiramate-have been recently added to the pharmacological arsenal for obesity treatment and could represent important tools to manage this epidemic disease. To achieve satisfactory anti-obesity goals, the use of these new medicines should be optimized and tailored to specific patient subpopulations also by applying dose adjustments if needed. In the present review, we posit that gender could be among the factors influencing the activity of the new obesity drugs both because of pharmacokinetic and pharmacodynamic factors. Although evidence from premarketing clinical studies suggested that no dose adjustment by gender is necessary for any of these new medicines, these studies were not specifically designed to identify gender-related differences. This observation, together with the strong theoretical background supporting the hypothesis of a gender-dimorphic response, strongly call upon an urgent need of new real-life data on gender-related difference in the pharmacology of these new obesity drugs

Gut microbiota: a new path to treat obesity

Obesity is a multifactorial disease resulting in excessive accumulation of adipose tissue. Over the last decade, growing evidence has identified the gut microbiota as a potential factor in the pathophysiology of both obesity and the related metabolic disorders. The gut microbiota is known to protect gastrointestinal mucosa permeability and to regulate the fermentation and absorption of dietary polysaccharides, perhaps explaining its importance in the regulation of fat accumulation and the resultant obesity. The proposed mechanisms by which the gut microbiota could contribute to the pathogenesis of obesity and the related metabolic diseases include: (a) a high abundance of bacteria that ferment carbohydrates, leading to increased rates of short-chain fatty acid (SCFA) biosynthesis, providing an extra source of energy for the host, that is eventually stored as lipids or glucose; (b) increased intestinal permeability to bacterial lipopolysaccharides (LPS), resulting in elevated systemic LPS levels that aggravate low-grade inflammation and insulin resistance; (c) increased activity of the gut endocannabinoid system. Fecal transplantation studies in germ-free mice have provided crucial insights into the potential causative role of the gut microbiota in the development of obesity and obesity-related disorders. Diet +/- bariatric surgery have been reported to modulate the gut microbiota, leading to lean host phenotype body composition. This review aims to report clinical evidence for a link of the gut microbiota with human obesity and obesity-related diseases, to provide molecular insights into these associations, and to address the effect of diet and bariatric surgery on the gut microbiota, including colonic microbiota, as a potential mechanism for promoting weight loss

Endocrine Aspects of Environmental "Obesogen" Pollutants

Growing evidence suggests the causal link between the endocrine-disrupting chemicals (EDCs) and the global obesity epidemics, in the context in the so-called "obesogenic environment". Dietary intake of contaminated foods and water, especially in association with unhealthy eating pattern, and inhalation of airborne pollutants represent the major sources of human exposure to EDCs. This is of particular concern in view of the potential impact of obesity on chronic non-transmissible diseases, such as type 2 diabetes, cardiovascular disease, and hormone-sensitive cancers. The key concept is the identification of adipose tissue not only as a preferential site of storage of EDCs, but also as an endocrine organ and, as such, susceptible to endocrine disruption. The timing of exposure to EDCs is critical to the outcome of that exposure, with early lifetime exposures (e.g., fetal or early postnatal) particularly detrimental because of their permanent effects on obesity later in life. Despite that the mechanisms operating in EDCs effects might vary enormously, this minireview is aimed to provide a general overview on the possible association between the pandemics of obesity and EDCs, briefly describing the endocrine mechanisms linking EDCs exposure and latent onset of obesity