Therapeutic Advances in Endocrinology and Metabolism

BACKGROUND: South Asians (SA) constitute a quarter of the global population and are disproportionally affected by both type 2 diabetes (T2D) and heart failure. There remains limited data of the acceptability and efficacy of low-energy meal replacement plans to induce remission of T2D in SA. OBJECTIVES: The objective of this exploratory secondary analysis of the DIASTOLIC study was to determine if there was a differential uptake, glycometabolic and cardiovascular response to a low-energy meal replacement plan (MRP) between SA and White European (WE) people with T2D...

BACKGROUND: Metformin, which has been shown to be highly effective in treating type 2 diabetes (T2D), is also believed to be valuable for Alzheimer's disease (AD). Computer simulation techniques have emerged as an innovative approach to explore mechanisms. OBJECTIVE: To study the potential mechanism of metformin action in AD and T2D. METHODS: The chemical structure of metformin was obtained from PubChem. The targets of metformin were obtained from PubChem, Pharm Mapper, Batman, SwissTargetPrediction, DrugBank, and PubMed...

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...

BACKGROUND: As a part of metabolic syndrome, hyperuricemia has a higher incidence in patients with diabetes than in the general population owing to various underlying factors. OBJECTIVES: The objective of the present study was to investigate the prevalence of hyperuricemia among patients with diabetes and identify associated factors. DESIGN: A cross-sectional study. METHODS: Herein, we included patients with diabetes managed at nine healthcare centers in Chenghua District, Chengdu, from February 2021 to November 2021...

Estrogen plays a prominent role in regulating and coordinating energy homeostasis throughout the growth, development, reproduction, and aging of women. Estrogen receptors (ERs) are widely expressed in the brain and nearly all tissues of the body. Within the brain, central estrogen via ER regulates appetite and energy expenditure and maintains cell glucose metabolism, including glucose transport, aerobic glycolysis, and mitochondrial function. In the whole body, estrogen has shown beneficial effects on weight control, fat distribution, glucose and insulin resistance, and adipokine secretion...

The different types of diabetes differ in disease pathogenesis but share the impairment or loss of β-cell function leading to chronic hyperglycaemia. While immune cells are present throughout the whole pancreas in normality, their number and activation is increased in diabetes. Different patterns and composition of inflammation could be observed in type 1, type 2 and type 3c diabetes. Immune cells, pancreatic stellate cells and fibrosis were present in the islet microenvironment and could add to β-cell dysfunction and therefore development and progression of diabetes...

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...

BACKGROUND: Endometriosis is an oestrogen-dependent disease that can cause subfertility in women who may require assisted reproductive technology (ART) to achieve their pregnancy goals. OBJECTIVES: The aim of this study was to compare ART outcomes in women with endometriosis following the long GnRH-agonist controlled ovarian stimulation (COS) protocol with those taking the GnRH-antagonist COS protocol. DATA SOURCES AND METHODS: MEDLINE, Embase and Web of Science were systematically searched in June 2022...

Hyponatremia is one of the most common lab abnormalities seen in clinical practice. It has become widely accepted that hypothyroidism is a cause of euvolemic hyponatremia. The primary mechanism is thought to be due to impaired free water excretion and changes in sodium handling in the kidney. However, the clinical studies are conflicting and do not definitively confirm the association between hypothyroidism and hyponatremia. Therefore, if severe hyponatremia occurs in a patient without myxedema coma, other potential etiologies should be sought...

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...

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...

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...

Transgender and nonbinary individuals are historically underserved by healthcare systems. A crucial area for improvement is fertility preservation counseling and service delivery, as gender-affirming hormone therapy and gender-affirming surgery may negatively affect future fertility. The methods available for fertility preservation depend on the patient's pubertal status and utilization of gender-affirming therapies, and counseling and delivery of these services are complex and require a multidisciplinary approach...

Accumulating evidence demonstrates the link between glucose and bone metabolism. The receptor activator of nuclear factor-kB ligand (RANKL)/the receptor activator of NF-κB (RANK)/osteoprotegerin (OPG) axis is an essential signaling axis maintaining the balance between bone resorption and bone formation. In recent years, it has been found that RANKL and RANK are distributed not only in bone but also in the liver, muscle, adipose tissue, pancreas, and other tissues that may influence glucose metabolism...

The syndrome of inappropriate antidiuresis (SIAD), the commonest cause of hyponatraemia, is associated with significant morbidity and mortality. Tolvaptan, an oral vasopressin V2-receptor antagonist, leads through aquaresis to an increase in serum sodium concentration and is the only medication licenced in Europe for the treatment of euvolaemic hyponatraemia. Randomised controlled trials have shown that tolvaptan is highly efficacious in correcting SIAD-related hyponatraemia. Real-world data have confirmed the marked efficacy of tolvaptan, but they have also reported a high risk of overly rapid sodium increase in patients with a very low baseline serum sodium...

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...

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...

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Hyponatraemia is common in patients with stroke and associated with adverse outcomes and increased mortality risk. The present review presents the underlying causes and provides a thorough algorithm for the diagnosis and management of hyponatraemia in stroke patients. Concomitant diseases and therapies, such as diabetes, chronic kidney disease and heart failure, along with diuretics, antidepressants and proton pump inhibitors are the most common causes of hyponatraemia in community. In the setting of acute stroke, the emergence of hyponatraemia might be attributed to the administration of hypotonic solutions and drugs (ie...

Nonbinary individuals, or those who identify outside of the traditional gender binary, are currently present in up to 9% of the general population of youth or up to 55% of gender-diverse youth. Despite the high numbers of nonbinary individuals, this population continues to experience barriers to healthcare due to providers' inability to see beyond the transgender binary and lack of competence in providing nonbinary care. In this narrative review, we discuss using embodiment goals to individualize care of nonbinary individuals, and review hormonal and nonhormonal treatment options for gender affirmation...