Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01275 (glucagon)
 26,492 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Diabetic ketoacidosis is a serious metabolic condition that may occur in patients with either Type 1 or Type 2 diabetes. The accumulation of ketoacids in the serum is a consequence of insulin deficiency and glucagon excess. Sodium Glucose Transporter 2 (SGLT2) inhibitors are novel therapeutic treatments for improving glucose homeostasis in patients with diabetes. Through reductions in glucose reabsorption by the kidney, they lower serum glucose in patients with Type 2 diabetes and they improve glucose control whether used alone or in combination with other therapies. Mechanistically, these drugs increase serum ketoacids and increase glucagon production, which in some individuals, can lead to formation of diabetic ketoacidosis. This review will first focus in how the kidney normally handles ketoacids, and second will discuss how the SGLT2 inhibitors affect the kidney in such a way so as to enhance the risk for development of ketoacidosis in susceptible individuals.
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PMID:Diabetic ketoacidosis, sodium glucose transporter-2 inhibitors and the kidney. 2724 May 41

Type 2 Diabetes Mellitus (T2DM) is a chronic illness with high prevalence in Mexico, Latin- America, and the world and is associated to high morbidity, disability, and mortality rate, especially in developing countries. T2DM physiopathology is very complex; insulin resistance in the muscle, liver, and adipose tissue, a reduction in the production of incretins (mainly GLP-1) in the intestine, increased glucagon synthesis, an insufficient response of insulin generation, and increased glucose reabsorption in the kidney lead all together to an hyperglycemic state, which has been closely associated with the development of micro and macrovascular complications. Sodium Glucose Linked Transporter 2 inhibitors (SGLT2i) are the most recent therapeutic class available for treating T2DM. SGLT2i central effect is a glycosuric action, and they can reverse the deleterious effect of tubular reabsorption of glucose in the diabetic patient resulting in greater hyperglycemia. Because their mechanism of action is completely different to current drugs, they can be considered as monotherapy or in combination with any other oral or parenteral medication, including different types of insulin or its analogues. This therapeutic synergy accomplishes a greater percentage of patients achieving glycemic control goals.
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PMID:SGLT2 Inhibitors in Diabetes Mellitus Treatment. 2776 8

Non-Alcoholic Fatty Liver Disease (NAFLD), the most common liver disease, is characterized by accumulation of fat (>5% of the liver tissue), in the absence of alcohol abuse or other chronic liver diseases. Its prevalence is increasing because of obesity, metabolic syndrome or Type 2 Diabetes Mellitus (T2DM). NAFLD can cause liver inflammation and progress to Non-Alcoholic Steatohepatitis (NASH), fibrosis, cirrhosis or Hepatocellular Cancer (HCC). Nevertheless, Cardiovascular Disease (CVD) is the most common cause of morbidity and mortality in NAFLD/NASH patients. Current guidelines suggest the use of pioglitazone both in patients with T2DM and in those without. The newer antidiabetic drugs such as Glucagon Like Peptide-1 Receptor Agonists (GLP-1 RA), Sodium-Glucose co- Transporter-2 inhibitors (SGLT2i), and statins plus ezetimibe, are considered safe by the guidelines, and may have a beneficial effect on NAFLD/NASH as well as Cardiovascular Disease (CVD) morbidity and mortality. Future drugs seem to have a potential for holding down the evolution of NAFLD and reduce liver- and CVD-related morbidity and mortality, but they will take some years to be approved for routine use. Until then pioglitazone, GLP-1 RA, SGLT2i, and statins plus ezetimibe, especially in combination might be useful for treating the huge number of patients with NAFLD/NASH.
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PMID:What Does the Future Hold for Non-Alcoholic Fatty Liver Disease and Non-Alcoholic Steatohepatitis? 3141 44

The recent results of Cardiovascular Outcomes Trials (CVOTs) in type 2 diabetes have clearly established the cardiovascular (CV) safety or even the benefit of two therapeutic classes, Glucagon-Like Peptide-1 receptor agonists (GLP-1 RA) and Sodium-Glucose Co-Transporter-2 inhibitors (SGLT-2i). Publication of the latest CVOTs for these therapeutic classes also led to an update of ESC guidelines and ADA/EASD consensus report in 2019, which considers using GLP-1 RA or SGLT-2i with proven cardiovascular benefit early in the management of type 2 diabetic patient with established cardiovascular disease (CVD) or at high risk of atherosclerotic CVD. The main beneficial results of these time-to event studies are supported by conventional statistical measures attesting the effectiveness of GLP-1 RA or SGLT2i on cardiovascular events (absolute risk, absolute risk difference, relative risk, relative risk reduction, odds ratio, hazard ratio). In addition, another measure whose clinical meaning appears to be easier, the Number Needed to Treat (NNT), is often mentioned while discussing the results of CVOTs, in order to estimating the clinical utility of each drug or sometimes trying to establish a power ranking. While the value of the measure is admittedly of interest, the subtleties of its computation in time-to-event studies are little known. We provide in this article a clear and practical explanation on NNT computation methods that should be used in order to estimate its value, according to the type of study design and variables available to describe the event of interest, in any randomized controlled trial. More specifically, a focus is made on time-to-event studies of which CVOTs are part, first to describe in detail an appropriate and adjusted method of NNT computation and second to help properly interpreting NNTs with the example of CVOTs conducted with GLP-1 RA and SGLT-2i. We particularly discuss the risk of misunderstanding of NNT values in CVOTs when some specific parameters inherent in each study are not taken into account, and the following risk of erroneous comparison between NNTs across studies. The present paper highlights the importance of understanding rightfully NNTs from CVOTs and their clinical impact to get the full picture of a drug's effectiveness.
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PMID:Computing and interpreting the Number Needed to Treat for Cardiovascular Outcomes Trials : Perspective on GLP-1 RA and SGLT-2i therapies. 3240 55

The advent of Sodium Glucose Transporter 2-inhibitors (SGLT2-i) in recent years gave endocrinologists the opportunity to actively treat and prevent heart failure (HF) in patients with type 2 diabetes (T2DM). While the relationship between T2DM and HF has been extensively reviewed, previous works focused mostly on epidemiology, pathophysiology and treatment of HF in T2DM. The aim of our work was to aid health care professionals in identifying individuals at high risk for this dreadful complication. Recent guidelines recommend to use drugs with proven cardiovascular benefits (Glucagon-like peptide-1 receptor agonists (GLP1-RA) and SGLT2-i) in patients with previous cardiovascular disease (CVD) and to prefer SGLT2-i in patients with known HF. In everyday clinical practice, the choice between these two drug classes in patients without known HF or atherosclerotic CVD is mostly arbitrary and based on the side effect profile. Recently, risk stratification tools to estimate HF incidence have been developed in order to guide treatment with a view to bring precision medicine into diabetes care. With this purpose, we provide a review of the tools able to predict HF incidence for patients in primary CVD prevention as well as risk of future hospitalizations for patients with known HF.
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PMID:Risk stratification tools for heart failure in the diabetes clinic. 3247 28