Autophagy, a relevant process for metabolic health and type-2 diabetes / Autofagia, un proceso relevante para la salud y la diabetes tipo 2

Autophagy is a very active process that plays an important role in cell and organ differentiation and remodelling, being a crucial system to guarantee health. This physiological process is activated in starvation and inhibited in the presence of nutrients. This short review comments on the three types of autophagy: macroautophagy, microautophagy, and chaperone-mediated autophagy, as well as different aspects that control autophagy and its relationship with health and degenerative diseases. As autophagy is highly dependent on functional autophagy (ATG) proteins integrating the phagophore, the role of some key ATG genes and epigenes are briefly commented on. The manuscript deepens discussing some central aspects of type-2 diabetes mellitus and their relationship with the cell cleaning process and mitochondria homeostasis maintenance, as well as the mechanisms through which antidiabetic drugs affect autophagy. Well-designed studies are needed to elucidate whether autophagy plays a casual or causal role in T2DM. (AU)

La autofagia es un proceso muy activo que juega un papel importante en la diferenciación y remodelación de células y órganos, siendo un sistema crucial para garantizar la salud. Este proceso fisiológico se activa en la inanición y se inhibe en presencia de nutrientes. En esta breve revisión se definen los tres tipos de autofagia: macroautofagia, microautofagia y autofagia mediada por chaperonas, y los diferentes aspectos que controlan la autofagia y su relación con la salud y las enfermedades degenerativas. Como la autofagia depende en gran medida de las proteínas funcionales de autofagia (ATG) que integran el fagóforo, se comenta brevemente el papel clave de algunos genes y epigenes de las ATG. El manuscrito profundiza discutiendo algunos aspectos centrales de la diabetes mellitus tipo 2 (DMT2) y su relación con el proceso de limpieza celular y el mantenimiento de la homeostasis mitocondrial, así como los mecanismos a través de cuales los fármacos antidiabéticos afectan a la autofagia. Se necesitan estudios bien diseñados para dilucidar si la autofagia juega un papel de casualidad o causalidad en el desarrollo de la DMT2. (AU)

Autophagy, a relevant process for metabolic health and type-2 diabetes.

Introduction: Autophagy is a very active process that plays an important role in cell and organ differentiation and remodelling, being a crucial system to guarantee health. This physiological process is activated in starvation and inhibited in the presence of nutrients. This short review comments on the three types of autophagy: macroautophagy, microautophagy, and chaperone-mediated autophagy, as well as different aspects that control autophagy and its relationship with health and degenerative diseases. As autophagy is highly dependent on functional autophagy (ATG) proteins integrating the phagophore, the role of some key ATG genes and epigenes are briefly commented on. The manuscript deepens discussing some central aspects of type-2 diabetes mellitus and their relationship with the cell cleaning process and mitochondria homeostasis maintenance, as well as the mechanisms through which antidiabetic drugs affect autophagy. Well-designed studies are needed to elucidate whether autophagy plays a casual or causal role in T2DM.

Introducción: La autofagia es un proceso muy activo que juega un papel importante en la diferenciación y remodelación de células y órganos, siendo un sistema crucial para garantizar la salud. Este proceso fisiológico se activa en la inanición y se inhibe en presencia de nutrientes. En esta breve revisión se definen los tres tipos de autofagia: macroautofagia, microautofagia y autofagia mediada por chaperonas, y los diferentes aspectos que controlan la autofagia y su relación con la salud y las enfermedades degenerativas. Como la autofagia depende en gran medida de las proteínas de autofagia funcional (ATG) que integran el fagóforo, se comenta brevemente el papel clave de algunos genes y epigenes de las ATG. El manuscrito profundiza discutiendo algunos aspectos centrales de la diabetes mellitus de tipo 2 (DMT2) y su relación con el proceso de limpieza celular y el mantenimiento de la homeostasis mitocondrial, así como los mecanismos a través de cuales los fármacos antidiabéticos afectan a la autofagia. Se necesitan estudios bien diseñados para dilucidar si la autofagia juega un papel de casualidad o causalidad en el desarrollo de la DMT2.

Executive Summary from Expert consensus on effectiveness and safety of iDPP-4 in the treatment of patients with diabetes and COVID-19.

BACKGROUND: This consensus aims to clarify the role of Dipeptidyl Peptidase-4 inhibitors (iDPP-4) in managing patients with diabetes during the COVID-19 pandemic. MATERIALS AND METHODS: A PubMed bibliographic search was carried out (December 2019-February 2021). Oxford methodology was used for the evaluation of evidence and possible recommendations were established by consensus. RESULTS: Diabetes appears to be an independent factor in COVID-19 disease (evidence 2b). No increased risk of contagion with iDPP-4 is demonstrated (evidence 2b), and its use has been shown to be safe (evidence 2b). The use of this drug may present a specific benefit in reducing mortality, particularly in in-hospital use (evidence 2a), reducing admission to intensive care units (evidence 2b) and the need for mechanical ventilation (evidence 2b). CONCLUSIONS: The use of iDPP-4 appears to be safe in patients with COVID-19, and quality studies are needed to clarify their possible advantages further.

Diabetes mellitus e insuficiencia cardíaca: nuevas perspectivas en el tratamiento farmacológico / Diabetes and heart failure: new perspectives in pharmacological treatment

La Diabetes Mellitus (DM) y la Insuficiencia Cardíaca (IC) son enfermedades crónicas cuyas prevalencias han ido en aumento y que determinan una mayor mortalidad de los pacientes que las padecen. La relación de ambas enfermedades es conocida como "Miocardiopatía Diabética" (MD). Los eventos fisiopatológicos principales de la MD son el mal control glicémico, el aumento de captación de ácidos grasos por parte de las células cardiacas, la disfunción endotelial y la remodelación cardíaca. Los nuevos tratamientos, se han enfocado en tratar tanto el control glicémico como la remodelación cardíaca. Los principales exponentes de los fármacos antidiabéticos favorables para la IC en pacientes con DM son los inhibidores del cotransportador de Sodio-Glucosa renal SGLT2 (iSGLT2), y los agonistas del receptor de GLP-1 (aGLP-1). Otros fármacos de relevancia son los antagonistas del receptor de mineralocorticoides (aRMC). Se realiza una revisión de la fisiopatología y del manejo actualizado de la IC en pacientes con DM.

Diabetes Mellitus (DM) and Heart Failure (HF) are chronic diseases whose prevalences have risen and which increase patient mortality. The two diseases are inter-related in what is called "Diabetic Cardiomyopathy" (DC). The main pathophysiological characteristics of cardiomyopathy are poor glycemic control, a rise in the capture of fatty acids by cardiac cells, endothelial dysfunction and cardiac remodeling. The principal anti-diabetic medications beneficial for HF in DM patients are renal sodium-glucose cotransporter-2 inhibitors (SGLT2) and GLP-1 receptor agonists (GLP-1RAs). Other relevant medications are mineralocorticoid receptor antagonists (MRA). We review the pathophysiology and current management of HF in diabetic patients.

[Management of hyperglycaemia with non-insulin drugs in adult patients with type 2 diabetes]. / Manejo de la hiperglucemia con fármacos no insulínicos en pacientes adultos con diabetes tipo 2.

Treatment of diabetes mellitus type2 (DM2) includes healthy eating and exercise (150minutes/week) as basic pillars. For pharmacological treatment, metformin is the initial drug except contraindication or intolerance; in case of poor control, 8 therapeutic families are available (6 oral and 2 injectable) as possible combinations. An algorithm and some recommendations for the treatment of DM2 are presented. In secondary cardiovascular prevention, it is recommended to associate an inhibitor of the sodium-glucose cotransporter type 2 (iSGLT2) or a glucagon-like peptide-1 receptor agonist (arGLP1) in patients with obesity. In primary prevention if the patient is obese or overweight metformin should be combined with iSGLT2, arGLP1, or inhibitors of type4 dipeptidylpeptidase (iDPP4). If the patient does not present obesity, iDPP4, iSGLT2 or gliclazide, sulfonylurea, recommended due to its lower tendency to hypoglycaemia, may be used.

Observational studies with type 2 diabetes mellitus treatments in Spain: A systematic literature review.

The aim of this systematic literature review (SLR) was to provide an overview of the Spanish research landscape of observational studies conducted with antidiabetic drugs in T2DM patients, published in the last five years, with special focus on the objectives, methodology and main research areas. Twenty-two articles, corresponding to 20 studies, were included in the analysis. Around 82% of the studies employed a longitudinal study design, collected data retrospectively (72.7%), and were based on secondary data use (63.6%). Pharmacotherapeutical groups most frequently studied were insulin (31.8%) and DPP4i (13.6%). Analytic design was employed most in the studies (68.2%), followed by descriptive analysis (22.7%). In the top five of the most studied variables are those related to effectiveness assessed according to glycaemic control (91%), treatment patterns (82%), safety (hypoglycaemia) (59%), the identification of effectiveness predictive factors (45%) and effectiveness according to other control measures such as anthropometric control or cardiovascular risk factors (36%).

Safety of diabetes drugs in patients with heart failure. / Seguridad de los fármacos antidiabéticos en pacientes con insuficiencia cardiaca.

Heart failure (HF) and diabetes mellitus are 2 clinical conditions that often coexist, particularly in patients older than 65 years. Diabetes mellitus promotes the development of HF and confers a poorer prognosis. Hypoglycaemic agents (either by their mechanism of action, hypoglycaemic action or adverse effects) can be potentially dangerous for patients with HF. In this study, we performed a review of the available evidence on the safety of diabetes drugs in HF, focused on the main observational and experimental studies. Recent studies on cardiovascular safety have evaluated, although as a secondary objective, the impact of new hypoglycaemic agents on HF, helping us understand the neutrality, risks and potential benefits of these agents.

Antidiabetic drugs for stroke prevention in patients with type-2 diabetes. The neurologist's point of view. / Antidiabéticos en prevención de ictus en pacientes con diabetes tipo 2. El punto de vista del neurólogo.

To date, stroke prevention in patients with diabetes mellitus (DM) has been based on the control of other risk factors and comorbidities, as clinical trials aimed at intensive glycemic control have failed to prove the existence of any sort of benefit in reducing macrovascular complications. However, thanks to the FDA's requirement to evaluate the vascular risk of antidiabetic drugs, there has been significant progress in the knowledge of their benefits on the risk of vascular death, acute myocardial infarction and non-fatal stroke in patients with type 2 DM and high vascular risk. This implies the need to incorporate these drugs into the overall vascular prevention strategy in patients with DM who have already suffered a stroke. This manuscript is a critical, non-systematic review on the oral antidiabetics that have demonstrated any sort of effect on stroke risk, interpreting the results of the main clinical trials from the neurologist's point of view.

Recommendations on the effect of antidiabetic drugs in bone. / Recomendaciones sobre el efecto de los fármacos antidiabéticos en el hueso.

OBJECTIVE: To provide recommendations on the effect of antidiabetic drugs on bone fragility to help select the most adequate antidiabetic treatment, especially in diabetic patients with high risk of fracture. PARTICIPANTS: Members of the Bone Metabolism Working Group of the Spanish Society of Endocrinology. METHODS: The GRADE system (Grading of Recommendations, Assessment, Development, and Evaluation) was used to establish both the strength of recommendations and the quality of evidence. A systematic search was made in MEDLINE (Pubmed) using the following terms associated to the name of each antidiabetic drug: AND "osteoporosis", "fractures", "bone mineral density", "bone markers", "calciotropic hormones". Papers in English with publication date before 30 April 2016 were reviewed. Recommendations were jointly discussed by the Working Group. CONCLUSIONS: The document summaries the data on the potential effects of antidiabetic drugs on bone metabolism and fracture risk.

Do we need new treatments for type 2 diabetes?

Diagnosis of type 2 diabetes mellitus encompasses multiple pathophysiological and clinical situations. Type 2 diabetes mellitus is characterized by a long and changing natural history. Personal circumstances and preferences also condition the actual effectiveness and safety of drugs used. In recent decades, modern drugs have markedly expanded and improved therapeutic options. However, their effectiveness remains limited in clinical practice. The main objective of decreasing macrovascular complications is not fully proven. Adverse events, especially hypoglycemia and weight gain, are still frequent and decrease treatment adherence. The constant loss of endogenous islet cell reserve is the main determinant of the need for intensified therapies. Current treatments have failed to improve long-term beta cell mass/function. It is desirable to move forward to obtain new drugs that offer solutions sustainable in the long term. These drugs should be able to fit the individual circumstances and preferences of patients with diabetes mellitus.

Aspectos clínicos e farmacológicos do emprego do exenatide na terapêutica do diabetes mellitus tipo 2 / Clinical and pharmacological aspects of the use of exenatide for the treatment of type II diabetes mellitus

O papel do exenatide no tratamento do diabetes mellitus tipo 2 tem sido foco de intensa pesquisa. Este fármaco age como um agonista do glucagon-like peptide 1 (GLP-1), interagindo com o receptor GLP-1, estimulando a secreção de insulina pelas células ß. O exenatide também tem se mostrado altamente eficaz na redução da secreção do glucagon, esvaziamento gástrico e ingestão alimentar. Esta revisão apresenta os principais aspectos clínicos e farmacológicos do uso do exenatide em pacientes diabéticos tipo 2. Assim, concluiu-se que o exenatide representa um novo fármaco antidiabético, uma vez que estimula a secreção de insulina por um mecanismo diferente do apresentado pelas sulfoniluréias e metiglinidas (bloqueadores de canais de potássio). Além disso, enquanto todos secretagogos de insulina (incluindo os inibidores da dipepdil peptidase-4) promovem ganho de peso, o exenatide, ao contrário, favorece a perda de peso, por sua ação inibidora do apetite.

The role of exenatide in the treatment of type II Diabetes Mellitus has become the focus of intense research. This drug works as a glucagon-like peptide 1 (GLP-1) agonist as it interacts with GLP-1 receptor through the stimulation of the insulin secretion in ß cells. The exenatide also has presented to be highly effective to reduce glucagon secretion, gastric emptiness, and food intake. This review shows the major clinical and pharmacological aspects of using exenatide in type II Diabetes Mellitus patients. Thus, it was concluded that exenatide is a new antidiabetic drug; since exenatide stimulates insulin secretion by a different mechanism of sulfonylureas and metiglinides (potassium channels blockers). Moreover, in spite of the fact that all insulin secretagogues (including the dipeptidyl peptidase-4 inhibitors) in contrast exenatide promotes weight gain mediated by its inhibitory appetite action.