TouchREVIEWS in endocrinology最新文献

Non-alcoholic steatohepatitis (NASH) now represents one of the most prevalent forms of cirrhosis and hepatocellular carcinoma. A number of treatment agents have undergone assessment in humans following promising results in animal models. Currently, about 50 therapeutic agents are in various stages of development. Recently, however, there have been a number of exciting and positive developments in this landscape, although there are inherent challenges ahead. In this article, we review the aetiological and pathological basis of NASH progression and describe putative targets for current therapies. We also discuss some of the likely future directions and difficulties around this complex and challenging disease paradigm.

Diabetic kidney disease (DKD) is the leading cause of chronic and end-stage kidney disease worldwide. Its pathogenic mechanism is complex, and it can affect the entire structures of the kidneys such as the glomerulus, tubules and interstitium. Currently, the urinary albumin excretion rate and the estimated glomerular filtration rate are widely accepted as diagnostic criteria. However, some studies have reported a different or non-classical clinical course of DKD, with some patients showing declined kidney function with normal levels of albuminuria, known as the 'non-albuminuric DKD' phenotype. The pathogenesis of this phenotype remains unclear, but some clinical and pathological features have been postulated. This review explores the evidence regarding this topic.

The number of people living with type 2 diabetes (T2D) and its complications worldwide is increasing at an alarming rate. Fortunately, our understanding of the benefits of glucose-lowering agents from the sodium-glucose co-transporter-2 (SGLT2) inhibitor and glucagon-like peptide-1 (GLP-1) receptor agonist classes on cardiovascular and kidney outcomes is advancing; this means we now have new options to mitigate the risks of these complications in patients with T2D. The SGLT2 inhibitors have consistently demonstrated benefits on atherosclerotic cardiovascular disease (ASCVD), chronic kidney disease (CKD) and heart failure (HF) events in dedicated outcome trials. Large guidelines groups now recommend SGLT2 inhibitors as a standard of care in patients with T2D and comorbid ASCVD, CKD and/ or HF. Evolving evidence additionally indicates kidney and HF benefits of SGLT2 inhibitors in populations without diabetes. These agents likely provide heart and kidney benefits through multiple mechanisms, as their impact on heart and kidney outcomes cannot be fully explained by their direct metabolic effects. On-going work to elucidate the beneficial mechanisms at play with SGLT2 inhibitors will help further optimize these life-saving therapies in patients with and without T2D.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can lead to multiorgan dysfunction through pulmonary and systemic inflammation. Infection also affects the thyroid gland directly via cytopathological effects of the virus or indirectly through cytokines, complement systems and coagulation mechanisms. The thyroid gland regulates innate and adaptive immune systems by genomic and nongenomic pathways. During or after SARS-CoV-2 infection, Graves' disease and subacute thyroiditis might be triggered resulting in hyperthyroidism; alternatively, the effect of the virus on the hypophyseal.hypothalamic axis might cause central hypothyroidism. Severe cases of coronavirus disease 2019 (COVID-19) can present with hypoxia, which requires the use of dexamethasone. This can depress basal serum concentrations of 3,5,3'-triiodothyronine. Thyroid function should be monitored when using dexamethasone in patients with COVID-19. This article briefly reviews the direct and indirect effects of SARS-CoV-2 on the thyroid gland and function.

Gastrointestinal hormones are currently used to treat type 2 diabetes mellitus (T2D). Incretin preparations with gastric inhibitory polypeptide (GIP) activity or glucagon-like peptide-1 (GLP-1) provide new means for controlling blood glucose levels, body weight, and lipid metabolism. GIP, an incretin, has not been used due to lack of promising action against diabetes. However, recent studies have shown that GIP has an important effect on glucagon and insulin secretion under normoglycaemic conditions. Co-existence of GIP with GLP-1 and glucagon signalling leads to a stronger effect than that of GLP-1 stimulation alone. The development of a GIP/GLP-1R unimolecular dual agonist with affinity for both GIP and GLP-1 receptors is under investigation, and the drug is expected to be clinically available in the near future. Tirzepatide, a GIP/GLP-1R unimolecular dual agonist, regulates metabolism via both peripheral organs and the central nervous system. The SURPASS phase III clinical trials conducted for tirzepatide comprise 10 clinical trials, including five global trials and the global SURPASS-CVOT trial, with >13,000 patients with T2D (ClinicalTrials.gov Identifier: NCT04255433). The clinical application of tirzepatide as a therapy for T2D may provide new insights into diabetic conditions and help clarify the role of GIP in its pathogenesis.

Background: Anterior pituitary hormones in blood follow a circadian rhythm, which may be influenced by various factors such as intracranial pathologies. In cerebrospinal fluid (CSF), pituitary hormones have been collected only selectively and circadian rhythm has not yet been investigated. This pilot study analysed diurnal variations of anterior pituitary hormones in patients in neurocritical care to determine whether circadian rhythmicity exists in these patients. Possible influences of intracranial pathologies were also investigated. Blood and CSF concentrations were assessed simultaneously to explore the value of blood concentrations as a surrogate parameter for CSF levels.

Methods: Blood and CSF samples of 20 non-sedated patients were collected at 06:00, noon, 18:00 and midnight, and analysed for adrenocorticotropic hormone (ACTH), cortisol, thyroid-stimulating hormone (TSH) and insulin-like growth factor-1 (IGF-1) concentrations at each of the four time points. ACTH and IGF-1 were measured by sandwich chemiluminescence immunoassay. Cortisol and TSH were measured by electrochemiluminescence immunoassay.

Results: Results showed inconsistent circadian rhythms. Less than 50% of the patients showed a circadian rhythmicity of ACTH, cortisol, TSH or IGF-1. Significance of diurnal variations was only present for blood concentrations of TSH. Correlations between blood and CSF concentrations were strong for cortisol and TSH.

Conclusions: CSF concentrations were only in the measurable range in some of the patients. No clear circadian rhythmicity could be identified, except for TSH in blood. Absence of significant diurnal variations could be explained by the underlying pathologies or disturbing influences of the intensive care unit. Blood concentrations of cortisol and TSH may be suitable surrogate parameters for CSF.

Traditional continuous glucose monitoring and flash glucose monitoring systems are proven to lower glycated haemoglobin levels, decrease the time and impact of hypoglycaemia or hyperglycaemia and, consequently, improve the quality of life for children and adults with type 1 diabetes mellitus (T1DM) and adults with type 2 diabetes mellitus (T2DM). These glucose-sensing devices can generate large amounts of glucose data that can be used to define a detailed glycaemic profile for each user, which can be compared with targets for glucose control set by an International Consensus Panel of diabetes experts. Targets have been agreed upon for adults, children and adolescents with T1DM and adults with T2DM; separate targets have been agreed upon for older adults with diabetes, who are at higher risk of hypoglycaemia, and women with pregestational T1DM during pregnancy. Along with the objective measures and targets identified by the International Consensus Panel, the dense glucose data delivered by traditional continuous glucose monitoring and flash glucose monitoring systems is used to generate an ambulatory glucose profile, which summarizes the data in a visually impactful format that can be used to identify patterns and trends in daily glucose control, including those that raise clinical concerns. In this article, we provide a practical guide on how to interpret these new glucometrics using a straightforward algorithm, and clear visual examples that demystify the process of reviewing the glycaemic health of people with T1DM or T2DM such that forward-looking goals for diabetes management can be agreed.

Objective: To examine the accuracy of urine c-peptide creatinine ratio (UCPCR) for identifying the type of diabetes in appropriate clinical settings. Design: Systematic review of test accuracy studies on patients with different forms of diabetes. Data sources: Medline, Embase and Cochrane library databases from 1 January 2000 to 15 November 2020. Eligibility criteria: Studies reporting the use of UCPCR for diagnosing patients with type 1 diabetes mellitus (T1DM), type 2 diabetes mellitus (T2DM) and monogenic forms of diabetes (categorized as maturity-onset diabetes of the young [MODY]). Study selection and data synthesis: Two reviewers independently assessed articles for inclusion and assessed the methodological quality of the studies using the Quality Assessment of Diagnostic Accuracy Studies-2 tool, with input from a third reviewer to reach consensus when there was a dispute. Meta-analysis was performed with the studies reporting complete data to derive the pooled sensitivity, specificity and diagnostic odds ratio (DOR), and narrative synthesis only for those with incomplete data. Results: Nine studies with 4,488 patients were included in the qualitative synthesis, while only four of these (915 patients) had complete data and were included in the quantitative synthesis. All the studies had moderate risk of bias and applicability concerns. Meta-analysis of three studies (n=130) revealed sensitivity, specificity and DOR of 84.4% (95% confidence interval [CI] 68.1-93.2%), 91.6% (82.8-96.1%) and 59.9 (32.8-106.0), respectively, for diagnosing T1DM using a UCPCR cut-off of <0.2 nmol/mmol. For participants with T2DM (three studies; n=739), UCPCR >0.2 nmol/mmol was associated with sensitivity, specificity and DOR of 92.8% (84.2-96.9%), 81.6% (61.3-92.5%) and 56.9 (31.3-103.5), respectively. For patients with MODY in the appropriate clinical setting, a UCPCR cut-off of >0.2 nmol/mmol showed sensitivity, specificity and DOR of 85.2% (73.1-92.4%), 98.0% (92.4-99.5%) and 281.8 (57.5-1,379.7), respectively. Conclusions: Based on studies with moderate risk of bias and applicability concerns, UCPCR confers moderate to high sensitivity, specificity, and DOR for correctly identifying T1DM, T2DM and monogenic diabetes in appropriate clinical settings. Large multinational studies with multi-ethnic participation among different age groups are necessary before this test can be routinely used in clinical practice. Study registration: Protocol was registered as PROSPERO CRD42017060633.

Background: Indian patients with type 2 diabetes mellitus (T2D) constitute one-sixth of affected adults globally. Here, we evaluate the association of body mass index (BMI) with body fat percentage (BF%) and glycated haemoglobin (HbA1c) levels among patients with T2D in India. Method: This was a cross-sectional Indian registry study across 845 geographically diverse zones between December 2017 and August 2019. Results: Of 37,927 patients, 55.6% were men, with a mean ± standard deviation age of 54.2 ± 11.5 years and HbA1c of 8.3 ± 1.71%. Mean ± standard deviation BMI and BF% were 27.0 ± 4.6 kg/m2 and 32.0 ± 8.0%, respectively. Overall, 15.4% of patients were overweight, and 25.0% were obese. Despite fewer males (20.7%) having BMI-based obesity than females (31.2%), around three-quarters of both sexes had BF%-defined obesity (males 77.2%; females 71.2%). One-third of males (34.6%) and 41.9% of females had BF%-defined obesity despite normal BMI. The association was substantiated by a moderately significant correlation (r=0.51) between BMI and BF% in the overall population (p<0.0001). Conclusion: This pan-India registry presents a real-world reflection of the Asian Indian phenotype: high BF% despite lower BMI in people with T2D. This highlights the importance of primordial and primary prevention, and may guide decisions on the choice of agents for glycaemic control, with a preference for drugs that promote weight loss or are weight neutral.

Automated insulin delivery (AID) systems play an important role in the management of type 1 diabetes mellitus (T1DM). These systems include three components: a continuous glucose monitor (CGM), an insulin pump and an algorithm that adjusts the pump based on the CGM sensor glucose readings. They are not fully automated and still require the user to administer bolus insulin doses for food. Some AID systems have automatic correction boluses, while others only have automatic basal or background insulin adjustments. As CGM has become more accurate and the technology has evolved, AID systems have demonstrated improved glycaemic outcomes. The clinical evaluation of AID systems in randomized controlled trials and real-world studies have shown their utility in helping glycaemic management. In this review, we compare AID systems that are commercially available in the US and summarize the literature, with a special focus on time in range in T1DM. The review also discusses new AID systems on the horizon and explores considerations for personalized care.