Therapeutic Advances in Endocrinology and Metabolism最新文献

Objective: To evaluate (1) the metabolic and endocrine effects of metformin combined with exenatide versus only metformin treatments in patients with polycystic ovary syndrome (PCOS) and abdominal obesity (AO) and (2) to determine the molecular mechanisms by which the combined treatment acts on PCOS patients.

Design: Randomized controlled trial of PCOS patients with AO to receive combined treatment with metformin-exenatide or metformin alone, and network pharmacology of gene expression in PCOS patients under the combined exposure.

Setting: Tertiary teaching hospital.

Patients: Women with PCOS and AO who fulfilled the Rotterdam Criteria under combined treatment with daily cyclical ethinylestradiol (35 μg/day) and cyproterone acetate (2 mg/day).

Intervention: Patients were randomized to either combined oral metformin (1500 mg/day) and exenatide (2 mg weekly subcutaneous injection, n = 35 women) treatment or metformin alone (n = 31 women) for 12 weeks. Network pharmacological prediction of gene expression under the combined exposure was studied.

Main outcome measures: (1) Basal and after both treatments anthropometric, endocrine, and metabolic changes were compared. (2) Network pharmacological prediction and gene expression were studied in patients under metformin-exenatide treatment. Venn diagram and Markov Cluster Algorithm diagram of core targets for AO were applied to identify key targets.

Results: Both treatments displayed (1) reductions of total testosterone, insulin, and lipoprotein levels and (2) increases of high-density lipoprotein cholesterol and apolipoprotein A1. We identified PCOS, AO, and comorbid genes further intersected with 269 combination therapy genes. Network pharmacology identified 154 key PCOS genes for drug regulation, including 29 closely related to AO and metabolism.

Conclusion: Both treatments improved glucose and lipid metabolism, weakening insulin resistance and improving some biochemical indexes. Network pharmacology identified genes related to AO and metabolism in patients with PCOS under the metformin-exenatide treatment.

Trial registration: ClinicalTrials.gov NCT04029272.

Researchers looked at data from the largest and longest-running database of children with growth disorders who were treated with daily injections of a brand of growth hormone called Genotropin. The researchers used these data to better understand the safety and effectiveness of daily growth hormone treatment. Researchers showed that daily growth hormone treatment: ○ Increased the children's heights, measured after 1 year of treatment. This was seen for all of the growth disorders studied. ○ Increased growth in children of different ages, with higher growth seen in children who had begun treatment before they started puberty. ○ Allowed short children to reach an adult height within the normal range. This was true even for children who did not begin treatment until early adolescence. ○ Was safe. Only a very small percentage (3%) of children had any side effects related to growth hormone treatment, the most common of which was headaches. When children reach the end of puberty, their growth plates close and they are unable to grow any taller. Once this happens, growth hormone treatment cannot increase their growth further and treatment should be stopped. The purpose of this plain language summary is to help you to understand the findings from recent research. Somatropin is used to treat the conditions under study that are discussed in this summary. Approval varies by country; please check with your local healthcare provider for more details.The results of this study may differ from those of other studies. Health professionals should make treatment decisions based on all available evidence and not on the results of a single study.

Background: Type 2 diabetes mellitus (T2DM) poses a growing global health challenge, particularly among individuals aged 55 years and above, placing significant pressure on healthcare systems.

Objectives: This study aims to assess long-term trends in T2DM burden and its risk factors in this demographic from 1990 to 2021.

Design: We conducted a retrospective analysis of T2DM based on the latest 2021 Global Burden of Disease (GBD) database.

Methods: Utilizing data from the 2021 GBD Study, we analyzed T2DM incidence, prevalence, and disability-adjusted life years (DALYs) among individuals aged ⩾55 years, stratified by sex and age group. An autoregressive integrated moving average model was applied to forecast trends for 2022-2036.

Results: In 2021, there were 9,179,347 (95% uncertainty interval (UI), 7,905,452-10,626,325) T2DM cases among those aged 55 years and above. From 1990 to 2021, global incidence increased from 409.06 (95% UI, 349.86-477.48) to 617.73 (95% UI, 532.00-715.10) per 100,000 population; diabetes-related mortality rose from 81.55 (95% UI, 76.57-85.44) to 96.19 (95% UI, 88.62-102.11) per 100,000, and DALYs climbed from 2562.71 (95% UI, 2293.81-2926.77) to 3552.41 (95% UI, 3041.94-4200.97) per 100,000. The highest mortality increase was in low-middle sociodemographic index (SDI) regions, while high SDI regions saw declines. Eastern Europe reported the highest incidence rate among 21 regions, at 1218.43 per 100,000 (95% UI, 1083.02-1370.82). Environmental, occupational, and behavioral risks were major contributors to diabetes-related mortality in this age group. Projections estimate T2DM cases will rise from 9.3 million in 2022 to 12.3 million by 2036.

Conclusion: The global burden of diabetes in adults aged ⩾55 years has risen substantially from 1990 to 2021. As the population continues to age, urgent action is needed to address this growing disease burden.

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.