Therapeutic Advances in Endocrinology and Metabolism最新文献

Background/purpose: The artificial pancreas system is among the most advanced devices for blood glucose management and is known to improve patients' glycated hemoglobin levels and time spent within the target glucose range. However, the use of an artificial pancreas in children with type 1 diabetes (T1D) in China has not yet been reported.

Methods: A retrospective study was conducted involving patients diagnosed with T1D who used a do-it-yourself artificial pancreas system (DIYAPS). The main inclusion criteria were as follows: T1D diagnosis, age between 3 and 18 years, usage of an insulin pump, and continuous glucose monitoring records for at least 3 months. The exclusion criterion was any comorbid conditions that could interfere with the study. The primary outcomes measured were changes in hemoglobin A1c (HbA1c) and time in range (TIR) before and after the DIYAPS was used.

Results: A total of 41 people were included in the study, including 21 males and 20 females, with a mean age of 9.4 years (standard deviation: 2.9 years), a median duration of T1D of 1.5 years (1.1-2.3), and a median duration of insulin pump use of 1.1 years (0.8-1.7). Compared with the baseline period (pre-DIYAPS), after using a DIYAPS, the TIR increased from 72.4% (57.9-82.4) to 80.8% (73.6-87.5; p < 0.01), the TAR (>10 mmol/L) decreased from 16.0% (8.2-21.2) to 8.8% (5.2-14.4; p < 0.01), the fasting blood glucose decreased from 8.2 mmol/L (7.2-9.4) to 6.7 mmol/L (6.3-7.6; p < 0.01), and the HbA1c decreased from 6.6% (6.1-7.6) to 6.3% (5.9-6.9; p < 0.05). No diabetic ketoacidosis, severe hypoglycemia, or other adverse events occurred during the use of the DIYAPS.

Conclusion: DIYAPS is safe and effective in Chinese children with T1D, particularly in improving TIR.

Background: Practice of Open-source Android artificial pancreas systems (AAPS) among Chinese patients is increasing, but data on their effectiveness is lacking.

Objectives: This study evaluates the effectiveness of AAPS compared with sensor-augmented pump (SAP) therapy among people with type 1 diabetes (T1D) in China.

Design: A real-world, case-control study.

Methods: We conducted this study among patients with T1D who had used AAPS or SAP therapy for >3 months. Propensity score matching (1:1) based on onset age, duration, gender, and baseline tight glucose range (time in the tight glucose range (TITR) 70-140 mg/dL) was performed. Key glycemic outcomes were analyzed.

Results: One hundred forty-two T1D people using AAPS and 142 matched people receiving SAP therapy were included (56.00% female). Age and duration of T1D were 26.40 (interquartile range (IQR) 11.30-34.70) and 3.20 (IQR 0.87-9.12) years, respectively. Baseline TITR and time in the target glucose range (TIR) of 70-180 mg/dL were 57.10 ± 18.30% and 79.30% (IQR 68.50-88.30), respectively. After 3 months, the AAPS group had better TITR (60.52 ± 14.57% vs 56.20 ± 17.22%, adjusted difference, 3.91%; p < 0.05) and TIR (79.12 ± 11.24% vs 77.37% (IQR 64.51-85.87), adjusted difference, 3.42%; p < 0.001) compared with the control group. In addition, time in hypoglycemia was shorter in the AAPS group than in the control group during the study (4.05% (IQR 2.52-6.78) vs 5.68% (IQR 2.69-10.11); adjusted difference, -1.17%; p < 0.05). Stratified analysis showed females, with a baseline glucose management indicator (GMI) < 7% and those aged over 18 years benefit more in the AAPS group. After adjusting for age, gender, duration of T1D, and baseline GMI, logistic regression analysis showed the AAPS group had a higher percentage of TITR improvement >5% than that in the control group (odds ratio = 1.73, 95% confidence interval (1.03, 2.92), p < 0.05).

Conclusion: AAPS is associated with significant improvements in glycemic control, without increasing hypoglycemia, compared to SAP therapy.

Introduction: There is conflicting evidence regarding optimal glycaemic targets to reflect the legacy effect of hyperglycaemia in people with type 2 diabetes (T2D). We examined the risks of microvascular complications and hospital admission with glycated haemoglobin (HbA1c) levels from the diagnosis of T2D.

Methods: We identified individuals with incident T2D from 1998 to 2007 from the Clinical Practice Research Datalink and Hospital Episode Statistics. A composite microvascular outcome was defined as a new diagnosis of neuropathy, nephropathy or retinopathy. A multivariate time-varying Cox regression analysis was performed to assess the risk of microvascular disease associated with HbA1c at five different levels (1.0% (11 mmol/mol) intervals). HbA1c 6.5%-7.5% (48.0-58.9 mmol/mol) was defined as the reference.

Results: N = 172,869 (mean age 62.6 ± 14.0 years, 54.6% female) were analysed. Average follow-up was 11.2 years. The risk of microvascular disease increased with higher HbA1c levels, the highest risk in the ⩾9.6% (⩾81 mmol/mol; hazard ratio (HR): 1.29, 95% confidence interval (CI): 1.11-1.51) and the lowest in the <6.5% (<48.0 mmol/mol; HR: 0.94, 95% CI: 0.83-1.08). The risk of hospital admission suggested a U-shaped association with HbA1c, highest risk in the lowest (<6.5% (<48.0 mmol/mol); HR: 1.04, 95% CI: 1.01-1.07) followed by HbA1c groups (8.6%-9.6% (70.0-81.0 mmol/mol); HR: 1.02, 95% CI: 0.97-1.08) while the lowest risk for hospital admission was observed for targets with the reference group (target between 6.5% and 7.5%, (48.0-58.9 mmol/mol)).

Conclusion: The risk of microvascular complications was lowest when HbA1c levels were within the non-diabetic range and increased with higher HbA1c levels. The risk of hospital admission was significantly elevated in individuals with HbA1c levels below 6.5%, suggesting a potential U-shaped association, although the increased risk at higher HbA1c levels did not reach statistical significance. This highlights the importance of maintaining individualised HbA1c targets in the management of T2D from diagnosis to prevent these complications.

Fibrous dysplasia (FD) is a rare, benign skeletal disorder characterized by expansile, fibrotic bone lesions that replace normal bone, resulting in decreased bone strength, pain, and fractures. The clinical presentation of FD can vary widely, complicating the diagnosis. FD can manifest as monostotic (single bone) or polyostotic (multiple bones) disease and can occur independently or as part of McCune-Albright Syndrome (MAS), a genetic condition that includes café-au-lait skin hyperpigmentation and endocrine abnormalities. FD/MAS arises from activating mutations in the GNAS gene, leading to constitutive activation of the G_sα protein and elevated cAMP levels. Despite understanding the genetic cause of FD, effective treatments remain limited. Current management strategies focus primarily on symptom control following the most recent comprehensive guidelines published in 2019. This review highlights emerging pharmacologic treatments, including denosumab, a monoclonal antibody that has shown promise in reducing lesion size and pain in FD patients, and burosumab, a monoclonal antibody targeting FGF23, which reduces renal phosphate wasting and osteomalacia in FD patients. In addition, we review updates in advanced genetic testing techniques, such as cell-free DNA and direct lesion sampling for next-generation sequencing, which are promising methods for improving the diagnostic accuracy of FD. Finally, multimodal approaches for pain management in FD, including nonsteroidal anti-inflammatory drugs, bisphosphonates, and novel agents like cannabinoids, are being used alongside the traditional approaches with physical therapy and psychological support. Ongoing research aims to enhance our understanding of FD pathogenesis and develop targeted therapies that could potentially reverse disease progression. This review underscores the importance of implementing a multidisciplinary approach in the management of FD/MAS and finding new therapeutic approaches that will help address the diverse manifestations and improve the quality of life for patients.

Bone and mineral disorders are highly prevalent in solid organ transplant recipients. These patients are at high risk for osteoporosis and fragility fractures due to several pre- and post-transplant factors, including end-stage organ disease leading to chronic malnutrition and osteomalacia, as well as chronic immunosuppressive therapy that has direct adverse effects on bone remodeling. Low pre-transplant bone mineral density is associated with an increased risk for fragility fracture post-transplant. Furthermore, there is a precipitous loss of bone density within 6-12 months post-transplant due to a myriad of causal factors. In this review, we will elaborate on the treatment options and challenges in management of osteoporosis in solid organ recipients using vitamin D, calcium, bisphosphonates, denosumab, and osteoanabolic agents. The greatest body of evidence discusses the use of bisphosphonates, with most patients benefiting from early treatment.

Iatrogenic hypoglycaemia remains a major barrier to optimal glycaemic control required to prevent long-term complications in people with type 1 diabetes (pwT1D). Hypoglycaemia is the consequence of the interaction between absolute or relative insulin excess from treatment and compromised physiological defences against falling plasma glucose. With a longer duration of diabetes and repeated exposure to hypoglycaemia, pwT1D can develop impaired awareness of hypoglycaemia (IAH). IAH increases the risk of severe hypoglycaemia six-fold, causing significant morbidity, and, if left untreated, death. Over the last few decades, a stepwise change in diabetes management has been the introduction and widespread uptake of novel technologies, including continuous glucose monitoring (CGM) and automated insulin delivery (AID) systems. These technologies aim to improve glycaemic control whilst minimising hypoglycaemia. Alarms and safety functions, such as suspension of insulin delivery, can help to reduce the hypoglycaemia burden. This review examines the role of continuous glucose monitors and AID systems in managing IAH, exploring evidence for their impact on symptomatic awareness and identifying areas for future research. In conclusion, there is strong evidence that CGM and AID systems improve glycaemic control and reduce the hypoglycaemia burden. However, despite the use of these technologies, severe hypoglycaemic episodes are not entirely eliminated, and it remains unclear whether their implementation restores the physiological symptoms and counter-regulatory response to hypoglycaemia.

Background: In recent years, driven by the rapid advancement of proteomics research, numerous scholars have investigated the intricate associations between plasma proteins and various diseases. Thus, this study aimed to identify novel therapeutic targets for preventing and treating metabolic-related diseases through Mendelian randomization (MR).

Methods: This study primarily utilized the MR method, leveraging genetic data from multiple large-scale publicly available genome-wide association studies. We employed two-sample MR within this framework to assess the associations between 1001 plasma proteins and 5 metabolism-related diseases. Finally, we strengthen the robustness and reliability of the MR results by conducting a series of sensitivity analyses, including bidirectional MR, colocalization analysis, Cochran's Q test, and the MR-Egger intercept test.

Results: The results from the inverse variance weighted method revealed that, following false discovery rate correction, many plasma proteins are significantly associated with metabolic-related diseases. Genetically predicted risks vary across diseases: for coronary artery disease, from 0.82 FGR proto-oncogene, Src family tyrosine kinase (FGR) to 1.13 (interleukin-6); for obesity, from 0.992 (POLR2F) to 1.005 (PRKAB1); for osteoporosis, from 0.998 (AIF1) to 1.001 (CLC); for stroke, from 0.71 (TNFRSF1A) to 1.47 (TGM2); and for type 2 diabetes, from 0.79 (KRT18) to 1.47 (RAB37).

Conclusion: Our findings reveal numerous plasma proteins linked to metabolic-related diseases. These findings offer fresh insights into the etiology, diagnostics, and treatment of these conditions.

Introduction: Although measuring bone mineral density (BMD) with dual X-ray absorptiometry (DXA) represents the standard of diagnosis and management of osteoporosis, there is a significant number of fragility fractures occurring in young patients without low BMD. Recently, clinical risk tools included hip axis length (HAL), a geometric parameter derived from the hip DXA scan, as a predictor of hip fractures in older postmenopausal women. This study aims to evaluate the relationship between HAL and other cortical bone fractures in young postmenopausal, clinically healthy women.

Materials and methods: This study is a retrospective analysis of Lunar DXA scans of 206 normal or overweight Caucasian women aged 40-60, who had less than 10 years of menopause without secondary causes of osteoporosis, no prior osteoporosis diagnosis or medication, and no history of hip or vertebral fractures.

Results: The 15 fractured women displayed statistically greater HAL values compared to the 191 non-fractured subjects (109.43 ± 6.44 vs 104.81 ± 5.32 mm, p = 0.002), even though there were no significant differences in age, body mass index, or BMD. The difference in HAL remained significant after adjusting for lumbar spine (LS) BMD and height (108.49 ± 1.23 vs 104.88 ± 0.34 mm, p = 0.005). HAL proved to be a fair indicator of non-hip, non-vertebral cortical fractures (area under curve = 0.720, p = 0.003), with a sensitivity of 86.7% and a specificity of 55.5%.

Conclusion: HAL was positively associated with non-hip, non-vertebral cortical bone fragility fractures in young postmenopausal, clinically healthy women and had significantly greater values in the fractured subgroup even after adjusting for LS BMD and height.

Rituximab (RTX) is a humanized chimeric anti-CD20 monoclonal antibody that leads to immunosuppression through rapid depletion of B lymphocytes. It has been demonstrated to be useful in treating both thyroid eye disease (TED) and myasthenia gravis (MG), respectively. However, the effectiveness of RTX in concurrent TED and MG cases is unclear and not previously reported in the literature. In this study, we describe a 13-year-old girl who presented with a 10-year history of general MG and a 1-year history of Graves' disease, bilateral proptosis, eye motility restriction, and lagophthalmos. A comprehensive evaluation confirmed the diagnosis of concurrent TED and MG. Satisfactory effectiveness was observed after RTX treatment without side effects. Based on the described observations, we suggest that RTX should be further explored as a treatment option for patients with concurrent TED and MG.

Medullary thyroid carcinoma (MTC) is a rare neuroendocrine tumor accounting for less than 5% of all thyroid cancers. An estimated 25% of cases are familial secondary to a germline mutation on the rearranged during transfection proto-oncogene (RET); this gene can be present as a somatic mutation in approximately 40%-60% of sporadic MTC tumors. There is an existing genotype-phenotype correlation in the clinical behavior of MTC, with the RET M918T variant associated with aggressive disease. The current systemic treatment profile for progressive metastatic MTC involves antiangiogenics multikinase inhibitors (MKI), specifically cabozantinib and vandetanib, and high-specific RET inhibitor therapy. Decisions on the timing of systemic therapy initiation in this population should involve multidisciplinary care and individualization on a case-by-case scenario; a comprehensive evaluation of performance status, tumor burden, progression rate, medical comorbidities, possible medication interactions, and goals of care must be considered in a patient-centered approach. This review summarizes the evidence on the safety, efficacy, and limitations of systemic therapies for MTC; the aim is to empower clinicians with the knowledge to optimally manage patients with advanced, progressive, or metastatic MTC.