Postgraduate medicine
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Postgraduate medicine · Nov 2020
Relationships among pancreatic beta cell function, the Nrf2 pathway, and IRS2: a cross-sectional study.
This study aimed to investigate the relationships among islet function, the Nrf2 pathway, and insulin receptor substrate 2 (IRS2) in type 2 diabetes mellitus (T2DM), prediabetes mellitus (IGR), and normal glucose tolerance (NGT) populations. ⋯ Upon impairment of glucose regulation, the expression of TNF-α in the human body increased, which indicated the aggravation of oxidative stress (OS) and the inflammatory response. Islet function was maintained in the pre-diabetic population, and concurrently, the TNF-α, Nrf2, and HO-1 levels were moderately elevated, the expression of IRS2 was marginally inhibited, and the Nrf2 pathway was activated under mild OS stimulus to resist OS, inflammation, and injury, which may have been mediated through PI3 K/AKT. In patients with T2DM, islet function was significantly poorer, TNF-α amplification was enhanced significantly, and Nrf2, HO-1, and IRS2 expression reduced significantly; this suggested that, along with the aggravation of OS and the inflammatory response, Nrf2 pathway activation and HO-1 expression were both inhibited, the antioxidant capacity of the body was reduced, IRS2 degradation increased, and islet function was impaired.
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Postgraduate medicine · Nov 2020
ReviewIntegrating oral semaglutide into clinical practice in primary care: for whom, when, and how?
Oral semaglutide is the first US Food and Drug Administration-approved oral glucagon-like peptide-1 receptor agonist (GLP-1RA) for the treatment of type 2 diabetes (T2D). Prior articles within this supplement reviewed the PIONEER trial program, which demonstrated that oral semaglutide reduced glycated hemoglobin and body weight when given to patients with uncontrolled T2D on various background therapies, and had a safety profile consistent with subcutaneous GLP-1RAs. This article provides guidance on integrating oral semaglutide into clinical practice in primary care. ⋯ Those managing patients should be aware of the potential impact of these dosing conditions on concomitant medications. When counseling patients, it is important to discuss these administration instructions, realistic therapeutic expectations, and strategies for mitigation of gastrointestinal events. Oral semaglutide provides a new option for add-on to initial T2D therapy (or later in the treatment paradigm), with the potential to enable more patients to benefit from the improvements in glycemic control, reductions in body weight, and low risk of hypoglycemia afforded by GLP-1RAs.
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Postgraduate medicine · Nov 2020
Editorial ReviewInterventional pain management in patients with cancer-related pain.
Invasive interventional procedures for managing pain in cancer patients are often underutilized following the popularization of the WHO analgesic ladder. The procedures that were successfully used until then were relegated away from mainstream palliative care practice, with the advent of newer opioids and adjuvants. Even though nerve blocks, intrathecal pumps and spinal cord stimulation were reintroduced as the fourth step of the WHO ladder, often referrals for these procedures are too late to produce a meaningful effect on quality of life. ⋯ ITDDs, neuromodulation and ever-increasing use of procedures routinely used in treating chronic nonmalignant pain would be the mainstay of interventional management until AI and nanotechnology would open doors for novel treatment options. Interventions should not be used as a last resort after multiple failed attempts at opioid therapy, but as an integral part of a management strategy including medical management, psychological and emotional welfare, and supportive care of the patient in a holistic manner. The curriculum of specialists should include appropriate training to safely perform and produce better quality evidence to validate the efficacy and safety of these challenging procedures.
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Postgraduate medicine · Nov 2020
Scientific independence and objectivity: many questions linger about treatment of type 2 diabetes, such as scientific study design, optimal glucose control and the safety of injecting exogenous insulin.
Whilst clinical guidelines exist for the treatment of people with type 2 diabetes, many underlying assumptions are still not qualified by convincing evidence. In this commentary, it is argued that fundamental issues still cloud clinical practice, such as biases in the design of clinical studies, the association between glucose control & clinical outcomes, and the safety of exposure to exogenous insulin and other glucose-lowering drugs. Relevant scientific evidence and alternative opinions about important issues continue to be largely ignored, and no effort has been made to resolve these questions. This may have had serious consequences, such as stifling innovation because there are no further benefits to be achieved in relation to glucose control.
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Postgraduate medicine · Nov 2020
ReviewGLP-1 receptor agonists in the treatment of type 2 diabetes: role and clinical experience to date.
Glucagon-like peptide-1 (GLP-1) is a hormone of the incretin system responsible for a variety of glucoregulatory effects, including glucose-dependent secretion of insulin and inhibition of glucagon release, the effects of which are impaired in people with type 2 diabetes (T2D). Targeting this deficiency using GLP-1 receptor agonists (GLP-1RAs) is a well-established approach in T2D, with over a decade of clinical experience now accrued. This article reviews the evidence for subcutaneous GLP-1RAs and their role in T2D treatment, and explores the rationale for an oral GLP-1RA from a primary care perspective. ⋯ Despite the known benefits of GLP-1RAs, adherence and persistence rates are suboptimal, potentially due in part to injection-related concerns. With some patients having a preference for oral medications, the development of an oral GLP-1RA is a logical approach to improving treatment options for patients with T2D. Co-formulation of semaglutide with an absorption enhancer has enabled the development and recent approval of the first oral GLP-1RA, oral semaglutide, which has the potential to expand use of GLP-1RAs in clinical practice.