Current Opinion in Endocrinology & Diabetes and Obesity最新文献

Purpose of review: The aim of this review was to discuss the use and concerns of diabetes agents, clinical targets, and key aspects to be considered in the management of patients with type 2 diabetes mellitus (T2DM), and at high risk or established cardiovascular disease (CVD).

Recent findings: The recent European and American guidelines recommended SGLT2 inhibitors and GLP-1 receptor agonists as the preferred first-line diabetes agents in patients with T2DM and CVD. This is a paradigm shift from using metformin as first-line therapy. Amid their widespread use, however, there are also concerns about their side effects. With the rapidly growing diabetes regimens available, questions arise about how best to approach the management of patients with T2DM and CVD.

Summary: To reduce CVD morbidity and mortality in patients with T2DM and at high or very high risk for CVD, the two key diabetes agents SGLT2i and/or GLP1-based therapies should be offered. Although lacking cardiovascular benefit, other diabetes agents remain necessary for many patients with T2DM for their glucocentric effects; Metformin and pioglitazone are useful in severe insulin resistance, while insulin therapy is often necessary in advanced diabetes; GLP1-RA is cautioned in patients with active gastrointestinal and mental health conditions, while DPP4 inhibitor is likely a well tolerated option in a challenging psychosocial setting. Other important aspects that should be considered include obesity, chronic kidney disease, women's cardiovascular health, and psychosocial factors.

Purpose of review: Obesity is recognized as a "gateway" chronic, progressive disease of dysfunctional adipocytes. Glucagon-like peptide-1 receptor agonist-based therapies (GLP1BTs), including glucagon-like peptide-1 receptor agonists (GLP-1 RAs) with/without glucose-dependent insulinotropic polypeptide (GIP), have demonstrated clinically significant weight loss and health gains in adults, hence interest in using them in younger and older people. Therefore, reviewing the role of GLP1BTs in these populations is pertinent and timely.

Recent findings: Recent American Pediatric Guidelines emphasize the need for early introduction of obesity-management medication (OMM). This review evaluates the recently published data evaluating use of GLP1BTs in young people with obesity and/or youth onset Type 2 diabetes (YOT2D).Large studies of GLP1BTs in adults included those over 65, however no separate trial has looked at this heterogeneous group. This review translates the evidence, as it pertains to those over 65 where possible.

Summary: Newer-generation GLP1BTs specifically target pathways involved in energy balance, glycaemic control and other metabolic functions, heralding a new era for the management of younger people.Published cardiovascular outcome trial (CVOT) data presented in this review support the utility of GLP1BTs in the management of older people living with obesity and/or Type 2 diabetes (T2D), with the reassurance of no new safety signals identified. Maturation of the longer-term data and publication of the additional CVOT data in cohorts of differing health complexity will provide further insights.

Purpose of review: The aim of this article was to review the up-to-date evidence with regards to the unique features of the Type 2 diabetes (T2D) pathophysiology, complications, response to therapy with the possibility of precision medicine guiding therapeutic decision making in Asia.

Recent findings: Asia is the epicenter of diabetes. There have been marked advances with genotyping and phenotyping of the Asian patient with T2D, particularly with young onset diabetes where early beta cell failure and rapid progression of complications are more frequent. As Asians have lower muscle mass and higher adiposity, sarcopenia is increasingly associated with diabetes. Response to lifestyle and pharmacotherapy are generally similar, but unique features exist with different populations. Across Asia, use of guideline directed medical therapy for cardio-renal protection are recommended, but uptake of these newer agents are suboptimal and barriers exist with regards to standardized care.

Summary: Although many similarities have been observed across Asia, due to the heterogeneity of populations within Asia, further research is required to streamline and pave the way towards precision medicine. There is an urgent need for region wide consensus to minimize barriers to diabetes care and stigma in diabetes terminology across Asia.

Purpose of review: This review highlights emerging evidence supporting the premise of precision diabetes care including but not limited to monogenic diabetes and discuss potential opportunities, challenges, and limitations for clinical adoption.

Recent findings: Driven by a single gene mutation, monogenic diabetes remains the best use-case for precision diabetes care. However, the increasing prevalence of diabetes among adolescents and young adults in an obesogenic environment makes triaging potential patients for genetic screening clinically challenging. High-dimensional molecular biomarkers (i.e., multiomics) can improve the risk prediction for incident type 2 diabetes (T2D), over and above a well established prediction model based on clinical variables alone. Machine learning approaches using clinical variable-based clustering methods have generated novel and reproducible T2D subgroups with distinct phenotypic and omics characteristics that are associated with differential long-term outcomes. This stratification-strategy may inform clinical decisions. However, on-going discussion and research will be needed to understand the clinical utility of sub-phenotyping T2D for precision care.

Summary: Precision diabetes care has extended from uncommon monogenic diabetes to T2D which will need more complex approaches like multiomics and machine-learning methods. The successful clinical translation will require cumulative evidence and close collaboration among the stake holders.

Purpose of review: The heart - brain axis (HBA) is the physiological interactions between the cardiovascular and nervous systems through autonomic nerves, hormones, and cytokines. Patients diagnosed with diabetes mellitus have an increased risk of the cardiovascular and neurological diseases. However, recent evidence demonstrated that different antidiabetic drugs may delay cognitive impairment and improve cardiovascular outcomes. This review examines the impact of antidiabetic drugs on the HBA in patients with diabetes.

Recent findings: Metformin improves the cardiovascular and cognitive outcomes through adenosine 5'-monophosphate-activated protein kinase activation. Sodium-glucose cotransporter-2 inhibitors reduce inflammation, oxidative stress by inhibiting the NLRP3 inflammasome thereby reducing the incidence of heart failure and formation of beta-amyloid and neurofibrillary tangles in the brain. Dipeptidyl peptidase-4 inhibitors exhibit neuroprotective effects in Alzheimer's disease by reducing amyloid-beta and tau pathology and inflammation but may exacerbate heart failure risk due to increased sympathetic activity and prolonged β-adrenergic stimulation. Glucagon-like peptide-1 receptor agonists exhibit neuroprotective effects in Alzheimer's and Parkinson's diseases by reducing neuroinflammation, but may increase sympathetic activity, potentially elevating heart rate and blood pressure, despite their cardioprotective benefits.

Summary: Antidiabetes medications have the potential to improve cardiovascular and cognitive outcomes; however, additional studies are required to substantiate these effects.

Purpose of review: Rates of unintended pregnancy have remained relatively stagnant for many years, despite a broad array of female contraceptive options. Recent restrictions on access to abortion in some countries have increased the urgency for expanding contraceptive options. Increasing data suggest men are keen to utilize novel reversible male contraceptives.

Recent findings: Despite decades of clinical research in male contraception, no reversible hormonal product currently exists. Nestorone/testosterone, among other novel androgens, shows promise to finally move to pivotal Phase 3 studies and introduction to the marketplace.

Summary: Hormonal male contraception utilizes androgens or androgen-progestin combinations to exploit negative feedback that regulates the hypothalamic-pituitary-testicular axis. By suppressing release of gonadotropins, these agents markedly decrease endogenous testosterone production, lower intratesticular testosterone and suppress spermatogenesis. The addition of a progestin enhances the degree and speed of sperm suppression. The androgen component preserves a state of symptomatic eugonadism in the male. There is growing demand and acceptance of male contraceptive options in various forms. As these formulations progress through stages of drug development, regulatory oversight and communication with developers around safety and efficacy standards and garnering industry support for advancing the production of male contraceptives will be imperative.

Purpose of review: Adolescents often have irregular menstrual cycles after menarche until the reproductive axis fully matures. This review explores how menstrual regularity is established and the health risks associated with prolonged time to cycle regularity in adolescents.

Recent findings: Cross-sectional studies show an association between prolonged time to cycle regularity in adolescents and increased risks for ongoing menstrual dysfunction, cardiometabolic disorders, cancers, and overall mortality. Importantly, some of these cardiometabolic associations are independent of PCOS status.

Summary: The menstrual cycle can be used as a vital sign for assessing overall health. While further longitudinal studies are needed to establish causal relationships, these findings highlight a crucial window for early intervention in adolescents with prolonged time to cycle regularity to mitigate future risks.

Purpose of review: The increasing rate of obesity is having an adverse impact on male reproduction.

Recent findings: The negative effect of reactive oxygen species on male reproductive tissues and the age of onset of obesity are new areas of research on male infertility.

Summary: This review highlights how obesity impairs male reproduction through complex mechanisms, including metabolic syndrome, lipotoxicity, sexual dysfunction, hormonal and adipokine alterations as well as epigenetic changes, and how new management strategies may improve the reproductive health of men throughout life.