To evaluate the residual effect of partial remission (PR) on immediate post-PR glycemic control according to its occurrence and duration in a cohort of children with type 1 diabetes mellitus (T1DM). Values of glycemic control parameters [i.e. HbA1C, insulin dose-adjusted hemoglobin A1C (IDAA1C), glycemic target-adjusted HbA1C (GTAA1C)] and data from glucose monitoring devices from 189 pediatric patients with new-onset type 1 diabetes were collected retrospectively from 24 months. Patients were characterized according to their remission status (PR+ and PR-). PR+ patients were subdivided into three subgroups regarding PR duration [i.e. short (⩾3-⩽6 months), intermediate (>6-⩽12 months), and long PR (>12-⩽14 months)]. We compared glycemic control data from each PR+ subgroup at +6 and +12 months post-PR with PR- patients at the same postdiagnosis time. Second, PR+ subgroups were compared with each other. PR+ patients showed improved glycemic control (i.e. HbA1C, IDAA1C, and GTAA1C) at + 6 months post-PR when compared with nonremitters (PR-), independently of the PR duration subgroups (p < 0.05). Interestingly, patients in long PR+ subgroup exhibited higher positive residual effect than short PR+ subgroup with lower GTAA1C scores (p = 0.02), better time in range (TIR) (p = 0.003), less time in hypoglycemia (10.45 versus 16.13%, p = 0.03) and less glycemic variability (83.1 mg/dl versus 98.84 mg/dl, p = 0.03). No significant differences were found for glucose control between PR+ and PR- patients at +12 months post-PR. This study supports the positive impact of PR occurrence and duration on short-term metabolic control (better HbA1C levels, IDAA1C and GTAA1C scores, TIR, and less glycemic variability) with the residual effect increasing according to PR duration.

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. mannitol and antiepileptics), poor solute intake, infections, as well as stroke-related conditions or complications, such as the syndrome of inappropriate secretion of antidiuretic hormone, cerebral salt wasting syndrome and secondary adrenal insufficiency. Diagnostically, the initial step is to differentiate hypotonic from non-hypotonic hyponatraemia, usually caused by hyperglycaemia or recent mannitol administration in patients with stroke. Determining urine osmolality, urine sodium level and volume status are the following steps in the differentiation of hypotonic hyponatraemia. Of note, specific parameters, such as fractional uric acid and urea excretion, along with plasma copeptin concentration, may further improve the diagnostic yield. Therapeutic options are based on the duration and symptoms of hyponatremia. In the case of acute or symptomatic hyponatraemia, hypertonic saline administration is recommended. Hypovolaemic chronic hyponatremia is treated with isotonic solution administration. Although fluid restriction remains the first-line treatment for the rest forms of chronic hyponatraemia, therapies increasing renal free water excretion may be necessary. Loop diuretics and urea serve this purpose in patients with stroke, whereas sodium-glucose transport protein-2 inhibitors appear to be a promising therapy. Nevertheless, it is yet unclear whether the appropriate restoration of sodium level improves outcomes in such patients. Randomized trials designed to compare therapeutic strategies in managing hyponatraemia in patients with stroke are required.

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. 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. Obese adults with T2D without symptomatic cardiovascular disease were allocated a low-energy (~810 kcal/day) MRP as part of the DIASTOLIC study (NCT02590822). Comprehensive multiparametric cardiovascular magnetic resonance imaging, echocardiography, cardiopulmonary exercise testing and metabolic profiling were undertaken at baseline and 12 weeks. A comparison of change at 12 weeks between groups with baseline adjustment was undertaken. Fifteen WE and 12 SAs were allocated the MRP. All WE participants completed the MRP versus 8/12 (66%) SAs. The degree of concentric left ventricular remodelling was similar between ethnicities. Despite similar weight loss and reduction in liver fat percentage, SA had a lower reduction in Homeostatic Model Assessment for Insulin Resistance [-5.7 (95% CI: -7.3, -4.2) versus -8.6 (-9.7, -7.6), p = 0.005] and visceral adiposity compared to WE [-0.43% (-0.61, -0.25) versus -0.80% (-0.91, -0.68), p = 0.002]. Exercise capacity increased in WE with no change observed in SA. There was a trend towards more reverse remodelling in WE compared to SAs. Compliance to the MRP was lower in SA versus WE. Overall, those completing the MRP saw improvements in weight, body composition and indices of glycaemic control irrespective of ethnicity. Whilst improvements in VAT and insulin resistance appear to be dampened in SA versus WE, given the small sample, larger studies are required to confirm or challenge this potential ethnic disparity. NCT02590822.

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.

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.

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.

Endometriosis is an oestrogen-dependent disease that can cause subfertility in women who may require assisted reproductive technology (ART) to achieve their pregnancy goals. 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. MEDLINE, Embase and Web of Science were systematically searched in June 2022. Randomized controlled trials (RCTs) and observational studies comparing the long GnRH-agonist COS protocol and the GnRH-antagonist COS protocol in women with all stages/subtypes of endometriosis were included. Data were synthesized into comprehensive tables for systematic review. The Scottish Intercollegiate Guidelines Network (SIGN) checklists were used for the risk of bias assessment of non-randomized studies and randomized studies, and all the included studies were deemed to have acceptable quality. Eight studies (one RCT and seven observational) with 2695 patients (2761 cycles) were included. Most studies generally reported non-significant differences in clinical pregnancy or live birth rates regardless of the COS protocol used. However, the GnRH-agonist protocol may yield a higher total number of oocytes retrieved, especially mature oocytes. Conversely, the GnRH-antagonist protocol required a shorter COS duration and lower gonadotrophin dose. Adverse outcomes, such as rates of cycle cancellation and miscarriage, were similar between both COS protocols. Both the long GnRH-agonist and GnRH-antagonist COS protocols generally yield similar pregnancy outcomes. However, the long GnRH-agonist protocol may be associated with a higher cumulative pregnancy rate due to the higher number of retrieved oocytes available for cryopreservation. The underlying mechanisms of the two COS protocols on the female reproductive tract remain unclear. Clinicians should consider treatment costs, stage/subtype of endometriosis and pregnancy goals of their patients when selecting a GnRH analogue for COS. A well-powered RCT is needed to minimize the risk of bias and compare the risk for ovarian hyperstimulation syndrome. This review was prospectively registered at PROSPERO under Registration No. CRD42022327604.

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.

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. First studies investigating the use of anti-inflammatory drugs demonstrate their ability to rescue remaining β-cell function and their potential benefit in diabetes treatment. This article provides an overview of immune cell infiltrates in different types of diabetes, highlights the knowledge of their impact on β-cell function and introduces the potential of immunomodulatory strategies.

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.