Glucagon-like peptide-1 (GLP-1) receptor agonists are a new class of antihyperglycemic drugs that enhance appropriate pancreatic β-cell secretion, pancreatic α-cell (glucagon) suppression, decrease ...liver glucose production, increase satiety through their action on the central nervous system, slow gastric emptying time, and increase insulin action on peripheral tissue. They are effective in the management of type 2 diabetes mellitus and have a favorable effect on weight loss. Their cardiovascular and renal safety has been extensively investigated and confirmed in many clinical trials. Recently, evidence has shown that in addition to the existing approaches for the treatment of obesity, semaglutide in higher doses promotes weight loss and can be used as a drug to treat obesity. However, some T2DM and obese patients do not achieve a desired therapeutic effect of GLP-1 receptor agonists. This could be due to the multifactorial etiologies of T2DM and obesity, but genetic variability in the GLP-1 receptor or signaling pathways also needs to be considered in non-responders to GLP-1 receptor agonists. This review focuses on the pharmacological, clinical, and genetic factors that may influence the response to GLP-1 receptor agonists in the treatment of type 2 diabetes mellitus and obesity.
Therapeutic peptides are oligomers or short polymers of amino acids used for various medical purposes. Peptide-based treatments have evolved considerably due to new technologies, stimulating new ...research interests. They have been shown to be beneficial in a variety of therapeutic applications, notably in the treatment of cardiovascular disorders such as acute coronary syndrome (ACS). ACS is characterized by coronary artery wall damage and consequent formation of an intraluminal thrombus obstructing one or more coronary arteries, leading to unstable angina, non-ST elevated myocardial infarction, and ST-elevated myocardial infarction. One of the promising peptide drugs in the treatment of these pathologies is eptifibatide, a synthetic heptapeptide derived from rattlesnake venom. Eptifibatide is a glycoprotein IIb/IIIa inhibitor that blocks different pathways in platelet activation and aggregation. In this narrative review, we summarized the current evidence on the mechanism of action, clinical pharmacology, and applications of eptifibatide in cardiology. Additionally, we illustrated its possible broader usage with new indications, including ischemic stroke, carotid stenting, intracranial aneurysm stenting, and septic shock. Further research is, however, required to fully evaluate the role of eptifibatide in these pathologies, independently and in comparison to other medications.
SGLT2 (sodium-glucose cotransporter 2) inhibitors are a new class of antihyperglycaemic drugs that act on the proximal tubules of the kidney. They have shown efficacy in the management of diabetes ...mellitus type 2 and their cardiovascular and renal safety have been extensively investigated and confirmed in clinical trials. However, inter-individual differences in response to treatment with SGLT2 inhibitors may present in everyday clinical practice, and good predictors of glycemic response and the risk for adverse events in an individual patient are lacking. As genetic variability of SGLT2 may influence the treatment response, pharmacogenetic information could support the choice of the most beneficial treatment strategy in an individual patient. This review focuses on the clinical and genetic factors that may influence the treatment response to SGLT2 inhibitors in type 2 diabetes patients with comorbid conditions.
Diabetic kidney disease (DKD) is a severe and common complication and affects a quarter of patients with type 2 diabetes mellitus (T2DM). Oxidative stress and inflammation related to hyperglycemia ...are interlinked and contribute to the occurrence of DKD. It was shown that sodium-glucose cotransporter-2 (SGLT2) inhibitors, a novel yet already widely used therapy, may prevent the development of DKD and alter its natural progression. SGLT2 inhibitors induce systemic and glomerular hemodynamic changes, provide metabolic advantages, and reduce inflammatory and oxidative stress pathways. In T2DM patients, regardless of cardiovascular diseases, SGLT2 inhibitors may reduce albuminuria, progression of DKD, and doubling of serum creatinine levels, thus lowering the need for kidney replacement therapy by over 40%. The molecular mechanisms behind these beneficial effects of SGLT2 inhibitors extend beyond their glucose-lowering effects. The emerging studies are trying to explain these mechanisms at the genetic, epigenetic, transcriptomic, and proteomic levels.
Diabetes mellitus is a devastating chronic metabolic disease. Since the majority of type 2 diabetes mellitus patients are overweight or obese, a novel term-diabesity-has emerged. The gut-brain axis ...plays a critical function in maintaining glucose and energy homeostasis and involves a variety of peptides. Amylin is a neuroendocrine anorexigenic polypeptide hormone, which is co-secreted with insulin from β-cells of the pancreas in response to food consumption. Aside from its effect on glucose homeostasis, amylin inhibits homeostatic and hedonic feeding, induces satiety, and decreases body weight. In this narrative review, we summarized the current evidence and ongoing studies on the mechanism of action, clinical pharmacology, and applications of amylin and its analogs, pramlintide and cagrilintide, in the field of diabetology, endocrinology, and metabolism disorders, such as obesity.
Surgical patients should receive perioperative thromboprophylaxis based on risk assessment, and the Caprini score is validated for this purpose. Whether the Padua score, originally devised for ...medical patients, can be useful in surgical patients remains to be fully clarified. This study aimed to evaluate perioperative thromboprophylaxis based on the Caprini or the Padua score in elective abdominal surgery. A total of 223 patients undergoing elective abdominal surgery for malignant or benign disease were prospectively evaluated. The patients were divided into two groups in which thromboprophylaxis was prescribed according to either the Caprini score (n = 122) or the Padua score (n = 101). Patients with high-risk scores in both groups received nadroparin. The alternate risk score in each group was calculated for evaluation purposes only. During a 3-month follow-up, we assessed patients for symptomatic venous thromboembolism (VTE), bleeding, or mortality. In the Caprini score group, 87 patients (71%) had a high risk for VTE (≥5 points), while 38 patients (38%) had a high risk for VTE (≥4 points) in the Padua score group; p < 0.00001. The overall correlation between the Caprini and Padua scores was moderate (r= 0.619), with 85 patients having high Caprini and discordant Padua scores. Ten patients died during follow-up (4.5%), and five developed non-fatal symptomatic VTE (2.2%). Among the five major bleeding incidents recorded (1.8%), two cases were possibly associated with pharmacological thromboprophylaxis. The incidence of adverse outcomes did not differ between the two groups. The odds ratio for adverse outcomes was significantly higher with a high Caprini or Padua risk score, malignant disease, age ≥65 years, and active smoking. We found no significant differences in adverse outcomes between abdominal surgical patients who received perioperative thromboprophylaxis based on either the Caprini or the Padua risk score. However, a discordant Padua score was noted in almost 40% of patients who had a high Caprini score, suggesting that the latter may be more sensitive than the Padua score in surgical patients.
This systematic review extensively investigated the role of the genetic and transcriptomic factors in late complications of type 2 diabetes mellitus (T2DM) and the current approaches targeting ...oxidative-stress-related pathways with antioxidant therapies. To cover our broad research area, we have conducted two systematic searches, the first focusing on genetic and transcriptomic factors affecting oxidative stress and the second one focusing on the antioxidant therapies in late complications of T2DM. The final review included 33 genetic and transcriptomic studies and 23 interventional randomized clinical trials. The conducted systematic review highlights the important role of oxidative stress in the development of late complications in T2DM patients. However, the current level of evidence does not support the use of genetic and transcriptomic factors as predictive and prognostic biomarkers for the development of T2DM late complications. Further studies are needed to elucidate the potential of targeting oxidative-stress-related pathways for novel preventative and therapeutic approaches. Additionally, antioxidants both in dietary and supplement form have been shown to improve different metabolic and biochemical parameters in T2DM patients with developed late complications. In recent years, studies have improved in methodological quality despite still mainly focusing on microvascular late complications of T2DM. Furthermore, the observed interventional studies suggest non-homogeneity in the duration of observation. As many studies do not provide post-intervention follow-up testing, it is difficult to assess the long-term health benefits of antioxidant supplementation.
Superior mesenteric artery embolisation is the most common cause of acute mesenteric ischaemia. Superior mesenteric artery embolisation can be caused by various cardiac diseases (myocardial ischaemia ...or infarction, atrial tachyarrhythmias, endocarditis, cardiomyopathies, ventricular aneurysms and valvular disorders), arterial aneurysms, ulcerated atherosclerotic plaques of the major arteries and others. A case of 65-year-old, previously healthy man with superior mesenteric artery embolism, who was found to also have mural aortic thrombi, is presented. The patient underwent an emergency procedure; small intestine and cecum were resected and jejuno-ascendo anastomosis was performed. The patient was put on lifelong anticoagulation therapy. Neither cardiac diseases nor arterial aneurysms were detected. There were no signs of underlying atherosclerosis. Work-up for antiphospholipid antibodies and rheumatic diseases was negative. Tumour markers were within normal levels and blood cultures were negative. This case represents the challenges in recognising an underlying cause of acute mesenteric embolism and highlights the importance of multidisciplinary diagnostic and treatment approach.
The significance of nutritional care in the management of cancer, particularly in the surgical treatment of abdominal cancer, is increasingly acknowledged. Body composition analysis, such as the ...Bioelectric impedance assay (BIA), and functional tests,
handgrip strength, are used when assessing nutritional status alongside general and nutritional history, clinical examination, and laboratory tests. The primary approach in nutritional care is individually adjusted nutritional counselling and the use of medical nutrition, especially oral nutritional supplements. The aim of the study was to investigate the effects of perioperative nutritional care on body composition and functional status in patients with carcinoma of the gastrointestinal tract, hepatobiliary system, and pancreas.
47 patients were included, 27 received preoperative and postoperative nutritional counselling and oral nutritional supplements (Group 1), while 20, due to surgical or organisational reasons, received nutritional care only postoperatively (Group 2). The effect of nutritional therapy was measured with bioimpedance body composition and handgrip measurements.
Group 2 had a higher average Nutritional Risk Screening (NRS) 2002 score upon enrolment (3 vs. 2 points); however, there was no difference when malnutrition was assessed using Global Leadership in Malnutrition (GLIM) criteria. There was a relative increase in lean body mass and fat-free mass index (FFMI) 7 days after surgery in group 1 (+4,2% vs. -2,1% in group 2). There was no difference in handgrip strength.
Our results indicate that combined preoperative and postoperative nutritional care is superior to only postoperative nutritional care. It seems to prevent statistically significant lean mass loss 7 days after surgery but not after 14 days or 4 weeks.
Besides good glycemic control, also control of lipid levels can effectively prevent or delay late type 2 diabetes (T2D) complications. As apolipoprotein E (APOE) and paraoxonase 1 (PON1) were shown ...to suppress atherosclerosis, we investigated the associations of common functional PON1 and APOE polymorphisms with plasma lipid levels and the risk for late complications in T2D patients.
Our retrospective genetic association study included 181 T2D patients genotyped for PON1 rs622, PON1 rs854560, APOE rs429358 and APOE rs7412.
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