Glucagon-like Peptide 1, Glucose-Dependent Insulinotropic Polypeptide, and Glucagon Receptor Agonists in Metabolic Dysfunction-Associated Steatotic Liver Disease: Novel Medication in New Liver Disease Nomenclature.

Glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are incretins that regulate postprandial glucose regulation, stimulating insulin secretion from pancreatic ß-cells in response to food ingestion. Modified GLP-1 receptor agonists (GLP-1RAs) are being administered for the treatment of obesity and type 2 diabetes mellitus (T2DM). Strongly related to those disorders, metabolic dysfunction-associated steatotic liver disease (MASLD), especially its aggressive form, defined as metabolic dysfunction-associated steatohepatitis (MASH), is a major healthcare burden associated with high morbidity and extrahepatic complications. GLP-1RAs have been explored in MASH patients with evident improvement in liver dysfunction enzymes, glycemic control, and weight loss. Importantly, the combination of GLP-1RAs with GIP and/or glucagon RAs may be even more effective via synergistic mechanisms in amelioration of metabolic, biochemical, and histological parameters of MASLD but also has a beneficial impact on MASLD-related complications. In this current review, we aim to provide an overview of incretins' physiology, action, and signaling. Furthermore, we provide insight into the key pathophysiological mechanisms through which they impact MASLD aspects, as well as we analyze clinical data from human interventional studies. Finally, we discuss the current challenges and future perspectives pertinent to this growing area of research and clinical medicine.

Restless Legs Syndrome masquerades as chronic insomnia.

OBJECTIVE: The objective of this study is to emphasize the importance of the clinical suspicion of Restless Legs Syndrome (RLS) among patients with chronic insomnia. METHODS: We conducted a retrospective study referring to the period 2009-2018. All patients presenting with the complaint of insomnia and fulfilling the criteria of Chronic Insomnia (C.I.) were enrolled. In this group we estimated how many patients finally had the diagnosis of RLS. Demographic and clinical characteristics (sleep related problems, fatigue, daytime sleepiness and psychological profile) were recorded and analyzed between C.I. and RLS patients using logistic regression models. RESULTS: A total of 532 patients presented with C.I. Among them 83 proved to have RLS. No differences in frequencies or odds were observed concerning the type of insomnia, daily fatigue, daytime sleepiness and depression. RLS is more frequent in women (p = 0.01) and in older patients (p = 0.05) who present with the picture of C.I. Anxiety levels are higher in the RLS group (p = 0.004). CONCLUSION: RLS and C.I. patients demonstrate a very similar profile which complicates the differential diagnosis. Physicians and especially psychiatrists who deal with insomnia must have increased clinical suspicion for RLS as RLS and insomnia have a totally different therapeutic approach.

Pre-Exercise Maltodextrin Ingestion and Transient Hypoglycemia in Cycling and Running.

This study examined the phenomenon of transient hypoglycemia and metabolic responses to pre-exercise carbohydrate (CHO) maltodextrin ingestion in cycling and running on the same individuals. Eleven active males cycled or ran for 30 min at 80% maximal heart rate (HRmax) after ingestion of either 1g/kg body mass maltodextrin (CHO-Cycle and CHO-Run respectively) or placebo (PL-Cycle and PL-Run) solutions. Fluids were ingested 30min before exercise in a double-blind and random manner. Blood glucose and serum insulin were higher before exercise in CHO (mean CHO-Cycle+CHO-Run) (Glucose: 7.4 ± 0.3 mmol·l-1; Insulin: 59 ± 10 mU·l-1) compared to placebo (mean PL-Cycle+PL-Run) (Glucose: 4.7 ± 0.1 mmol·l-1; Insulin: 8 ± 1 mU·l-1) (p<0.01), but no differences were observed during exercise among the 4 conditions. Mean blood glucose did not drop below 4.1 mmol·l-1 in any trial. However, six volunteers in CHO-Cycle and seven in CHO-Run experienced blood glucose concentration ≤ 3.5 mmol·l-1 at 20min of exercise and similar degree of transient hypoglycemia in both exercise modes. No association was found between insulin response to maltodextrin ingestion and drop in blood glucose during exercise. Blood lactate increased with exercise more in cycling compared to running, and plasma free fatty acids (FFA) concentrations were higher in placebo compared to CHO irrespective of exercise mode (p<0.01). The ingestion of maltodextrin 30min before exercise at about 80% HRmax produced similar glucose and insulin responses in cycling and running in active males. Lactate was higher in cycling, whereas maltodextrin reduced FFA concentrations independently of exercise mode.