Therapeutic Advances in Endocrinology and Metabolism最新文献

Recent studies suggest a possible association of hyponatremia with osteoporosis, falls and bone fractures. The objectives of this narrative review were to further explore this association and the related pathophysiological mechanisms and to suggest a practical approach to patients with osteoporosis or chronic hyponatremia in clinical practice. We conducted an extensive PubMed search until October 2022 with the combination of the following keywords: 'hyponatremia' or 'sodium' or 'SIADH' and 'fractures' or 'bone' or 'osteoporosis', as MeSH Terms. Review of numerous observational studies confirms a significant independent association of, even mild, hyponatremia with two- to three-fold increase in the occurrence of bone fractures. Hyponatremia is a risk factor for osteoporosis with a predilection to affect the hip, while the magnitude of association depends on the severity and chronicity of hyponatremia. Chronic hyponatremia also increases the risk for falls by inducing gait instability and neurocognitive deficits. Besides the detrimental impact of hyponatremia on bone mineral density and risk of falls, it also induces changes in bone quality. Emerging evidence suggests that acute hyponatremia shifts bone turnover dynamics towards less bone formation, while hyponatremia correction increases bone formation. The key unanswered question whether treatment of hyponatremia could improve osteoporosis and lower fracture risk highlights the need for prospective studies, evaluating the impact of sodium normalization on bone metabolism and occurrence of fractures. Recommendations for clinical approach should include measurement of serum sodium in all individuals with fracture or osteoporosis. Also, hyponatremia, as an independent risk factor for fracture, should be taken into consideration when estimating the likelihood for future fragility fracture and in clinical decision-making about pharmacological therapy of osteoporosis. Until it is proven that normalization of sodium can lower fracture occurrence, correcting hyponatremia cannot be universally recommended on this basis, but should be decided on a case-by-case basis.

Many transgender (trans) individuals utilize gender-affirming hormone therapy (GAHT) to promote changes in secondary sex characteristics to affirm their gender. Participation rates of trans people in sport are exceedingly low, yet given high rates of depression and increased cardiovascular risk, the potential benefits of sports participation are great. In this review, we provide an overview of the evidence surrounding the effects of GAHT on multiple performance-related phenotypes, as well as current limitations. Whilst data is clear that there are differences between males and females, there is a lack of quality evidence assessing the impact of GAHT on athletic performance. Twelve months of GAHT leads to testosterone concentrations that align with reference ranges of the affirmed gender. Feminizing GAHT in trans women increases fat mass and decreases lean mass, with opposite effects observed in trans men with masculinizing GAHT. In trans men, an increase in muscle strength and athletic performance is observed. In trans women, muscle strength is shown to decrease or not change following 12 months of GAHT. Haemoglobin, a measure of oxygen transport, changes to that of the affirmed gender within 6 months of GAHT, with very limited data to suggest possible reductions in maximal oxygen uptake as a result of feminizing GAHT. Current limitations of this field include a lack of long-term studies, adequate group comparisons and adjustment for confounding factors (e.g. height and lean body mass), and small sample sizes. There also remains limited data on endurance, cardiac or respiratory function, with further longitudinal studies on GAHT needed to address current limitations and provide more robust data to inform inclusive and fair sporting programmes, policies and guidelines.

As the transgender and gender diverse (TGD) population ages, more transfeminine and transmasculine individuals present to clinic to initiate or continue their gender-affirming care at older ages. Currently available guidelines on gender-affirming care are excellent resources for the provision of gender-affirming hormone therapy (GAHT), primary care, surgery, and mental health care but are limited in their scope as to whether recommendations require tailoring to older TGD adults. Data that inform guideline-recommended management considerations, while informative and increasingly evidence-based, mainly come from studies of younger TGD populations. Whether results from these studies, and therefore recommendations, can or should be extrapolated to aging TGD adults remains to be determined. In this perspective review, we acknowledge the lack of data in older TGD adults and discuss considerations for evaluating cardiovascular disease, hormone-sensitive cancers, bone health and cognitive health, gender-affirming surgery, and mental health in the older TGD population on GAHT.

Lifestyle changes should be the main basis for any treatment for metabolic dysfunction-associated fatty liver disease (MAFLD), aiming to increase energy expenditure, reduce energy intake and improve the quality of nutrients consumed. As it is a multifactorial disease, approaches such as physical exercise, a better dietary pattern, and possible pharmacological intervention are shown to be more efficient when used simultaneously to the detriment of their applications. The main treatment for MAFLD is a lifestyle change consisting of diet, activity, exercise, and weight loss. The variables for training prescription such as type of physical exercise (aerobic or strength training), the weekly frequency, and the intensity most indicated for the treatment of MAFLD remain uncertain, that is, the recommendations must be adapted to the clinical conditions comorbidities, and preferences of each subject in a way individual. This review addresses recent management options for MAFLD including diet, nutrients, gut microbiota, and physical exercise.

Charcot neuroarthropathy (CN) was first described over 150 years ago. Despite this there remains uncertanity around the factors that contribute to its development, and progression. This article will discuss the current controversies around the pathogenesis, epidemiology, diagnosis, assessment and management of the condition. The exact pathogenesis of CN is not fully understood, and it is likely to be multifactorial, with perhaps currently unknown mechanisms contributing to its development. Further studies are needed to examine opportunities to help screen for and diagnose CN. As a result of many of these factors, the true prevalence of CN is still largely unknown. Almost all of the recommendations for the assessment and treatment of CN are based on low-quality level III and IV evidence. Despite recommendations to offer people with CN nonremovable devices, currently only 40-50% people are treated with this type of device. Evidence is also lacking about the optimal duration of treatment; reported outcomes range from 3 months to more than a year. The reason for this variation is not entirely clear. A lack of standardised definitions for diagnosis, remission and relapse, heterogeneity of populations, different management approaches, monitoring techniques with unknown diagnostic precision and variation in follow-up times prevent meaningful comparison of outcome data. If people can be better supported to manage the emotional and physical consequences of CN, then this could improve people's quality of life and well-being. Finally, we highlight the need for an internationally coordinated approach to research in CN.

Diabetes (DM) increases fracture risk, and bone quality depends on type diabetes type, duration, and other comorbidities. Diabetes is associated with a 32% increased relative risk (RR) of total fractures and 24% increased RR of ankle fractures compared with patients without DM. Type 2 DM is associated with a 37% increased RR of foot fractures compared with patients without DM. The incidence of ankle fractures in the general population is 169/100,000 per year, while foot fractures occur less frequently, with an incidence of 142/100,000 per year. Biomechanical properties of bone are negatively impacted by stiff collagen, contributing to the increased risk of fragility fractures in patients with DM. Systemic elevation of proinflammatory cytokines, such as tumor necrosis factor-alpha (TNFα), interleukin-1β (IL-1β), and interleukin 6 (IL-6), impact bone healing in patients with DM. Fractures in patients with DM, can be associated with poorly regulated levels of RANKL (receptor activator of nuclear transcription factor kappa-b ligand) leading to prolonged osteoclastogenesis, and net bone resorption. One of the most salient factors in treating fractures and dislocations of the foot and ankle is to recognize the difference between patients with uncomplicated and complicated DM. Complicated diabetes is defined as 'end organ damage', and for the purposes of this review, includes patients with neuropathy, peripheral artery disease (PAD) and/or chronic renal disease. Uncomplicated diabetes is not associated with 'end organ damage'. Foot and ankle fractures in patients with complicated DM pose challenges, and surgery is associated with increased risks of impaired wound healing, delayed fracture healing, malunion, infection, surgical site infection, and revision surgery. While patients with uncomplicated DM can be treated like patients without DM, patients with complicated DM require close follow-up and robust fixation methods should be considered to withstand the anticipated prolonged healing period. The aims of this review are as follows: (1) to review pertinent aspects of DM bone physiology and fracture healing, (2) to review the recent literature on treatment of foot and ankle fractures in patients with complicated DM, and (3) to provide treatment protocols based on the recent published evidence.

Nonalcoholic fatty liver disease (NAFLD), once considered a benign condition, has been associated with several cardiometabolic complications over the past two decades. The worldwide prevalence of NAFLD is as high as 30%. NAFLD requires the absence of a "significant alcohol intake." Conflicting reports have suggested that moderate alcohol consumption may be protective; therefore, the diagnosis of NAFLD previously relied on negative criteria. However, there has been a significant increase in alcohol consumption globally. Apart from the rise in alcohol-related liver disease (ARLD), alcohol, a major toxin, is associated with an increased risk of several cancers, including hepatocellular carcinoma. Alcohol misuse is a significant contributor to disability-adjusted life years. Recently, the term metabolic dysfunction-associated fatty liver disease (MAFLD) was proposed instead of NAFLD to include the metabolic dysfunction responsible for the major adverse outcomes in patients with fatty liver disease. MAFLD, dependent on the "positive diagnostic criteria" rather than previous exclusion criteria, may identify individuals with poor metabolic health and aid in managing patients at increased risk of all-cause and cardiovascular mortality. Although MAFLD is less stigmatizing than NAFLD, excluding alcohol intake may increase the risk of already existing underreported alcohol consumption in this subgroup of patients. Therefore, alcohol consumption may increase the prevalence of fatty liver disease and its associated complications in patients with MAFLD. This review discusses the effects of alcohol intake and MAFLD on fatty liver disease.

Background: Patients with type 1 diabetes mellitus (T1DM) may have suboptimal glucose control and are interested in the use of adjuvant therapies.

Objectives: To determine, from the patients' perspective, the reasons for initiation of glucagon-like peptide 1 receptor agonist (GLP-1RA) and/or sodium glucose cotransporter 2 inhibitor (SGLT2i) in treating T1DM; perceived benefits/side effects, reasons for discontinuation, and willingness to reinitiate therapy.

Design: Retrospective chart review with structured telephone interviews.

Methods: We identified patients with T1DM treated with a GLP-1RA and/or SGLT2i for >3 months at University of Texas Southwestern Medical Center (Dallas, TX, USA) and Poznan University (Poznan, Poland). We conducted structured telephone interviews regarding their experiences.

Results: We interviewed 68 participants treated with GLP-1RA and 82 with SGLT2i. Treatment was initiated for improving glycemic control (as reported by 61.8% versus 81.7% of GLP-1RA and SGLT2i users, respectively), weight loss/appetite suppression (51.4% versus 23.2%) and to reduce insulin requirement (13.2% versus 11%). Most participants (86.8% of GLP-1RA and 89.0% of SGLT2i users) reported ⩾1 benefit attributed to therapy. Reported benefits were improved glycemic control (reported by 58.8% versus 82.9% of GLP-1RA and SGLT2i users, respectively), weight loss/appetite suppression (63.2% versus 30.5%), and reduced insulin requirement (27.9% versus 34.1%). More GLP-1RA users reported side effects versus SGLT2i users (63.2% versus 36.6%); 22.6% discontinued GLP-1RA due to side effects versus 11.0% SGLT2i users. Diabetic ketoacidosis (DKA) was reported by 4.9% of SGLT2i users, but none in GLP-1RA users. Of those who discontinued medication, 60.7% of GLP-1RA versus 56.0% of SGLT2i prior users were willing to reinitiate treatment.

Conclusions: Patients with T1DM report initiating adjuvant treatment with GLP-1RA and/or SGLT2i to improve glycemic control and lose weight; most patients reported perceived benefits from these therapies. Side effects (including DKA) are reported more commonly in real life than in clinical trials. Given patient interest in these medications, further studies should evaluate the long-term risk-benefits ratio in larger cohorts.

Over the last decade, metabolic-associated fatty liver disease (MAFLD) has become an important public health issue worldwide. In many countries, MAFLD has become the most common cause of chronic liver disease. On the contrary, hepatocellular carcinoma (HCC) mortality is rising. Liver tumors have become the third cause of cancer mortality worldwide. HCC is the most frequent liver tumor. While the burden of HCC related to viral hepatitis is declining, the prevalence of MAFLD-related HCC is rising rapidly. Classical screening criteria for HCC consider cirrhotic, advanced fibrosis, and viral hepatitis patients. Metabolic syndrome with liver involvement or MAFLD is associated with a higher risk of HCC development, even in the absence of cirrhosis. The question about the cost effectiveness of surveillance for HCC in MAFLD is yet not fully answered. There are no guidelines that address the question of when to start or how to define the population who can benefit of surveillance for HCC in MAFLD patients. This review aims to revise the evidence of HCC development in MAFLD. It hopes to be a step closer to defining screening criteria for HCC in MAFLD.

Aims: Patients' adherence to using knee-high offloading treatment is critical to effective healing of diabetes-related foot ulcers (DFUs). Previous studies have found that patients generally have low adherence to using removable knee-high offloading treatments, yet no study has investigated whether their adherence differs during daytime and nighttime. This study aimed to investigate the levels and factors associated with adherence to using knee-high removable cast walker (RCW) treatment during daytime and nighttime weight-bearing activities in people with DFUs.

Methods: This was a secondary analysis of data collected from a multi-centre cross-sectional study investigating adherence to using knee-high RCWs among 57 participants with DFUs. All participants had multiple socio-demographic, physiological and psychosocial factors collected, before having their adherence to using RCWs during weight-bearing activity monitored over a 1-week period using the dual activity monitor method. Adherence data were categorised into daytime (06:00-18:00) and nighttime (18:00-06:00) periods and calculated separately. Multiple linear regression was used to identify factors associated with daytime and nighttime adherence.

Results: Mean adherence to using RCW during weight-bearing activities in people with DFUs was higher during daytime compared with nighttime [39.9% (SD = 18.9) versus 20.4% (SD = 16.7), p < 0.001]. Factors independently associated with lower adherence during daytime were being male, longer diabetes duration, not having peripheral artery disease (PAD), and higher perceived RCW heaviness. Factors associated with lower adherence during nighttime were higher mean daytime steps, not having retinopathy and having dyslipidaemia.

Conclusions: Adherence to using RCWs during weight-bearing activities reduced significantly at nighttime compared with daytime among people with DFUs, and this was associated with different factors. Interventions to improve adherence, in research and clinical practice, should incorporate methods to target daytime or nighttime adherence specifically.