TouchREVIEWS in endocrinology最新文献

Insulin icodec is a once-weekly basal insulin analogue in late-phase clinical development. Similar efficacy and safety of icodec to once-daily basal insulin analogues have been reported in over 4,200 participants with type 2 diabetes from three phase II and five phase III trials. Indeed, glycated haemoglobin reduction was superior for icodec among insulin-naïve participants (ONWARDS 1, 3 and 5) and in those switching from a daily basal insulin in ONWARDS 2, with the latter trial demonstrating improved diabetes treatment satisfaction scores with insulin icodec versus insulin degludec.

Many new technologies have been developed over the past decade, and these have substantially changed the way diabetes is managed. Continuous glucose monitoring is now the standard of care for many people living with diabetes, and among its numerous benefits, it has been shown to improve glycaemic outcomes and enhance quality of life. Older adults carry a high burden of diabetes and have a high risk of hypo-glycaemia and hypo-glycaemic unawareness, and continuous glucose monitoring can help to improve glycaemic management in this vulnerable population. Unfortunately, only a few trials have evaluated the effectiveness of continuous glucose monitoring in older adults. Certainly, the implementation of continuous glucose monitoring in older adults can come with many challenges, including logistical, educational and reimbursement barriers. This article will discuss the benefits of continuous glucose monitoring in older adults with diabetes, the clinical studies that support its use and the barriers to its optimal implementation in this population.

Male hypogonadism affects 10-30% of the male population and is often under-recognized and under-treated. Different replacement formulations exist, each with specific benefits and limitations. These replacements include gels, patches and short- and long-acting injectables. JATENZO® (oral testosterone undecanoate; Clarus Therapeutics Inc., Northbrook, IL, US) is the first oral formulation of testosterone approved by the US Food and Drug Administration. TLANDO® (oral testosterone undecanoate; Lipocine Inc., Salt Lake City, UT, US), another oral testosterone formulation, has also recently been approved by the US Food and Drug Administration. Based on unique chemistry using a self-emulsifying drug delivery system and lymphatic absorption, JATENZO and TLANDO address some of the limitations of other dosing routes while providing a safe option without evidence of liver dysfunction. This review discusses various testosterone treatment options, focusing on the role and pharmacokinetics of the new oral formulations.

Statin use has been linked with new-onset diabetes mellitus (NODM). In the present systematic review, we aimed to determine the incidence of NODM with statin use by assessing and summarizing the data generated by different systematic reviews and metaanalyses published on this topic. We conducted a systematic review of systematic reviews and meta-analyses using a pre-defined study protocol. Two authors independently performed a literature search using PubMed, Embase and the Cochrane Central Register of Controlled Trials (CENTRAL) for studies reporting data on statin use and NODM incidence and screened and extracted data for the outcomes of interest. The Assessing the Methodological Auality of Systematic Reviews 2 (AMSTAR 2) checklist was used to evaluate the quality of the included systematic reviews and meta-analyses. The initial search yielded 621 potential records, and 16 relevant systematic reviews and meta-analyses were included in the present systematic review. The included studies showed an increase in the risk of NODM with statin use. In particular, rosuvastatin and atorvastatin were associated with NODM in many systematic reviews or meta-analyses; however, pravastatin and pitavastatin were found to be associated with lower or no risk. We observed a positive trend of development of NODM with statin use became more evident with advancing years as more number of studies were added. Intensive doses of statins and use in older subjects were found to be important risk factors for NODM. Finally, the quality assessment revealed that the included systematic reviews and metaanalyses were of critically low or low quality. We concluded that statin use carries a risk of causing NODM. Statins should not be discouraged in anticipation of NODM. However, glycaemic monitoring should be encouraged with the on-going statin therapy. Furthermore, clinical studies addressing the use of statins and the incidence of NODM as their primary objective should be planned.

For over 50 years, immunoassays have been extensively used to quantitate hormones in blood, other fluids and tissues. Each assay has its own sensitivity, specificity and other analytical components. Despite the differences between commercial products, these assays provide important clinical information about hormone levels in patients. However, inaccurate results can occur because of technical issues, as well as patient-specific factors that can interfere with immunoassay hormone measurements. The latter include excessive normal blood or serum components, the presence of cross-reacting substances, extremely high levels of hormones leading to the high-dose hook effect, and interference from a variety of endogenous factors such as human antibodies that interact with the assay components or high levels of biotin in the serum from exogenous ingestion. This article briefly reviews the sources and recognition of endogenous interference, and describes methods to determine the correct serum hormone concentration.

The most common malignancies in childhood are leukaemias, brain tumours, lymphomas, neuroblastomas, soft tissue sarcomas and kidney tumours. At present, about 80% of childhood cancers can be treated successfully, which has significantly increased long-term survival. Concomitantly, adult gonadal function in childhood cancer survivors has become a concern. However, the immediate effect of cancer and its management on the reproductive axis function has received less attention. We conducted a review of the effects of malignancies and their treatments on the gonadal axis during childhood and adolescence. Some results are controversial, probably because the analyses do not distinguish between the malignancy types, their treatments and/or the age at treatment. However, there is agreement that cancer can partially affect gonadal function before treatment, as revealed by low circulating levels of inhibin B and anti-Müllerian hormone. Subsequently, chemotherapy transiently impairs the somatic component of the gonads (i.e. testicular Sertoli cells and ovarian granulosa cells) with normalization after treatment ends. The impact of chemotherapy may persist through adulthood after more intensive chemotherapy regimens, radiotherapy and conditioning for haematopoietic stem cell transplantation, when there is a severe impairment of the somatic component of the gonads or of the stem germ cells.

Growth hormone provocation testing forms the cornerstone of the diagnosis of childhood growth hormone deficiency in clinical practice. Despite the widespread use of these tests, various criticisms have been levelled against them, such as the labour-intensive nature of the tests, their potential for serious adverse effects and their questionable reproducibility. Macimorelin acetate, a ghrelin mimetic approved for the diagnosis of adult growth hormone deficiency, could serve an unmet need in the diagnosis of childhood-onset growth hormone deficiency based on its good tolerability and benign side effect profile.

Pancreatic neuroendocrine tumours (pNETs) are a major manifestation of multiple endocrine neoplasia type 1 (MEN1), and the most significant cause of morbidity and mortality in this disorder. There is some evidence that the early use of somatostatin analogues can retard progression, especially of small non-functioning tumours, but there are no other prophylactic therapies for patients, and the treatment of metastatic disease is similar to that for sporadic pNETs. A recent study has shown that in cell line and animal models, MEN1 mutations lead to an upregulation of the enzyme dihydroorotate dehydrogenase (DHODH), which is involved in increasing precursor metabolites for the synthesis of pyrimidines. In these studies, blockade of this pathway by various means, including the DHODH inhibitor leflunomide, attenuates cell growth and tumour progression, suggesting a critical dependence on DHODH specifically in MEN1-mutated tissue. Preliminary clinical studies in three patients with MEN1 and pNETs have indicated some therapeutic potential of this drug, which has previously been used for some years in patients with rheumatoid arthritis. It is suggested that further clinical trials of this re-purposed drug are indicated to evaluate its potential for the treatment of patients with MEN1 and pNETS. This article describes the clinical problem of MEN1 and pNETs, and reviews the recent publication reporting on these initial results.

Patients with familial chylomicronaemia syndrome (FCS) have severe hypertriglyceridaemia due to genetically absent lipolytic capacity. They have a poor response to conventional therapies. To reduce the risk of potentially fatal pancreatitis, the management of FCS relies principally on a strict low-fat diet, which is difficult to follow and compromises quality of life. Targeted reduction of apolipoprotein C-III using new anti-APOC3 agents, such as the short interfering RNA ARO-APOC3, represents a promising approach to correct the severe biochemical disturbance in FCS.

The efficacy of statins in the primary and secondary prevention of cardiovascular disease has been proven beyond doubt. The number needed to treat to prevent one cardiovascular event is 1 in 30 over 10 years, and the number needed to treat for secondary prevention is much lower. However, a recent study demonstrated that only 68% of eligible patients are on statin therapy. Moreover, there seems to be a reluctance to escalate statin doses due to the fear of adverse effects. The adverse effects that worries patients and their physicians most frequently are those related to muscular symptoms. N-of-1 trial evidence suggests that muscular symptoms attributed to statins are often caused by the nocebo effect. This article aims to provide a structured, evidence-based approach to suspected statin-related muscle toxicity.