Therapeutic Advances in Endocrinology and Metabolism最新文献

Polycystic ovary syndrome (PCOS) is a prevalent disorder in the modern world, affecting around 6%-20% of females of childbearing age. Hormonal and metabolic symptoms vary over time but often arise throughout puberty. Treatment includes lifestyle interventions as a first line of treatment. In certain cases, specific medications may be considered. However, there is a growing interest in using Glucagon-like Peptide-1 Receptor Agonists (GLP-1RAs) in PCOS due to their efficacy in weight loss, insulin resistance, and heart health. Aside from the metabolic role of GLP-1RAs, which aids in the relief of PCOS symptoms, there is also the possibility of direct involvement in reproductive health in PCOS, including its role in the hypothalamic-gonadal axis, menstrual irregularity, ovulation, ovarian morphology, anti-inflammatory properties, and fertility. This review discusses the latest data on GLP-1RAs' metabolic and reproductive health benefits in PCOS. Moreover, this article covers pharmaceutical interactions and synergistic effects of drugs, including metformin and other medications, with GLP-1RAs. It also conveys an overview of recent clinical trials utilizing GLP-1RAs to treat PCOS.

Background and aims: During the COVID-19 pandemic confinement, virtual care strategies were implemented for individuals with type 2 diabetes (T2D). During the recovery process, hybrid care schemes (combining in-person and virtual care) continued, with limited information available on the results. This study aims to describe the metabolic parameters, lifestyle, self-care behaviors, and mental health of patients treated in the hybrid comprehensive care program.

Methods: This is a descriptive and longitudinal observational study in patients with T2D who attended the hybrid comprehensive care program, comprising baseline (face-to-face), 3-month follow-up (face-to-face), 1-year follow-up (virtual), and 2-year follow-up (face-to-face). Metabolic and mental health variables were obtained (presence of anxiety, affective and eating disorders, quality of life questionnaires, Hospital Anxiety and Depression Scale for depression and anxiety, problem areas in diabetes, and empowerment) as well as self-care variables: calories consumed, exercise time, self-monitoring blood glucose, and foot checks.

Results: Data from 104 patients were analyzed from October 2018 to November 2022, with a mean age of 55 (48-61) years, a female predominance of 49%, and a time since diagnosis of T2D of 2 (0-3) years. Metabolic parameters improved at 3 months, 1 year, and 2 years of follow-up. In self-care behaviors, the differences in minutes per week of exercise increased (baseline: 0 (0-180), 3 months: 175 (60-330), 1 year: 0 (0-150), and at 2 years: 90 (0-195); p < 0.0001). In self-care activities, we observed an increase in the proportion of patients who checked their feet and performed glucose self-monitoring (p < 0.001). A good quality of life, without distress and empowerment, has also improved.

Conclusion: During a comprehensive care hybrid program, patients could maintain metabolic control goals, engage in self-care behaviors, mainly foot care and glucose self-monitoring, and improve their mental health parameters.

Background: Tirzepatide (TZP) has demonstrated efficacy for glycemic control and weight loss in subjects with type 2 diabetes (T2D). However, previous clinical trials were not conducted under the treatment of glucagon-like peptide-1 receptor agonists (GLP-1RAs) as a background regimen nor were they limited to subjects with chronic kidney disease (CKD).

Objectives: We evaluated the glycemic control of tirzepatide switching from conventional GLP-1 receptor agonists in subjects with T2D and CKD.

Design: This was a prospective, two-arm, observational study performed at a single center.

Methods: Eligible subjects were individuals with T2D and CKD who had been treated with dulaglutide for more than 3 months, with glycated hemoglobin (HbA1c) ⩾7.0%, and an estimated glomerular filtration rate ⩽60 mL/min/1.73 m². Subjects who switched to tirzepatide (TZP group) and those who continued dulaglutide (Dula group) were observed over 6 months. The primary outcome was a change in HbA1c over 6 months between the groups. Additional metabolic parameters, including body weight and the urine albumin-creatinine ratio (UACR), were evaluated. Adverse events in the TZP group were also investigated.

Results: Of the 55 participants, 48 completed the study (TZP group, n = 23; Dula group, n = 25). Tirzepatide significantly reduced HbA1c and body weight compared with the Dula group over 6 months (both p < 0.01). UACR levels remained stable in the TZP group throughout the study period and increased significantly in the Dula group (p < 0.05). Gastrointestinal events and hypoglycemia were observed in the TZP group, and those subjects who suffered hypoglycemic symptoms were mostly insulin users.

Conclusion: Tirzepatide might be an effective alternative treatment for subjects with T2D and CKD who did not achieve sufficient glycemic control with conventional GLP-1RAs, as well as preventing the progression of nephropathy.

Trial registration: This study was registered with the University Hospital Medical Information Network (registration number UMIN 000051344, date: June 16, 2023). https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_his_list.cgi?recptno=R000058576.

Aims: Metabolic-associated fatty liver disease (MAFLD) is closely associated with insulin resistance (IR) and systemic inflammation. Apolipoprotein A1 (ApoA1) and Apolipoprotein B (ApoB), as notable non-traditional lipid markers, have demonstrated distinct advantages in identifying risks related to metabolic syndrome and coronary atherosclerosis, yet its association with MAFLD and the mediating roles of IR/inflammation remain unclear.

Methods: This retrospective investigation involved 1061 participants, categorized into a non-MAFLD group (n = 529) and an MAFLD group (n = 532). Univariate and multivariate logistic regression models, Spearman's correlation, and mediation analysis were utilized to explore the intricate associations between ApoB/ApoA1, MAFLD, inflammation, and IR.

Results: The MAFLD group exhibited markedly elevated levels of neutrophils/lymphocytes, neutrophils/platelets, systemic immune inflammation index, systemic inflammation response index, pan-immune-inflammation value and triglyceride-glucose index (TyG), TyG body mass index (TyGBMI), and metabolic score for insulin resistance (METS-IR) compared to the non-MAFLD group. Logistic regression analysis revealed that ApoB/ApoA1, TyG, TyGBMI, and METS-IR were markedly linked to MAFLD risk. Spearman's correlation analysis identified substantial positive links between ApoB/ApoA1 and TyG (r = 0.45), METS-IR (r = 0.47), and TyGBMI (r = 0.42). Mediation analysis, adjusted for confounding variables, revealed that TyG, TyGBMI, and METS-IR mediated 70.4%, 100%, and 100% of the association between ApoB/ApoA1 and MAFLD, respectively.

Conclusion: Our findings clarify the complex interrelationships between ApoB/ApoA1, MAFLD risk, inflammation, and IR, and for the first time, demonstrate that IR may act as a key potential mediator in the link between ApoB/ApoA1 and MAFLD, rather than systemic inflammation. This suggests that IR may serve a more prominent role than chronic systemic inflammation in the association between lipid metabolism and MAFLD risk, and intervening in IR may be more effective than anti-inflammatory therapy in blocking the progression from lipid metabolism disorders to MAFLD.

Continuous glucose monitoring (CGM) has revolutionized diabetes management globally, offering real-time insights into blood glucose levels and trends. In India, where diabetes prevalence is significant, the adoption of digital health tools (DHTs) for CGM has seen remarkable growth. However, successful integration and adoption of these DHTs require collaboration between healthcare professionals and individuals with diabetes. Ensuring the compatibility, accuracy, and reliability of CGM systems is imperative for optimizing diabetes management outcomes in India. Several challenges persist in adopting DHTs for CGM in the country. The adoption of ambulatory glucose profiles and CGM using DHTs has been transformative in diabetes clinics. This paper culminates with expert recommendations on integrating DHTs into diabetes clinics, focusing on training, communication, and technology utilization. The introduction of the Freestyle^® Libre into diabetes clinics demonstrates the system's influence and the advantages seen by both patients and healthcare professionals. With real-time data, improved patient interaction, real-world data for evidence-based practices, and the ability to support patients' and healthcare professionals' informed decision-making, these tools have the potential to completely transform the management of diabetes. The goal is to enhance diabetes care through digital health solutions, considering the unique healthcare landscape of India.

Background: Findings from our previous study indicate that people with type 1 diabetes mellitus (T1DM) unknowingly misinterpret data displayed on glucose monitoring systems and make inaccurate treatment decisions, which increases the risk of hospitalisation.

Objectives: This study aims to assess the effectiveness of incorporating textual descriptions in glucose monitoring systems compared to existing systems. The main goal is to minimise the effort required in glucose data interpretation, facilitating better self-management and ultimately improving haemoglobin A1C levels.

Methods: A two-arm and mixed-methods evaluation was conducted. Participants were randomly allocated to the control arm (existing systems) or the experimental arm (newly developed systems incorporating textual descriptions). In the first part, a task-based usability assessment was conducted to compare performance between the two arms. The second part evaluated participant preferences, agreement with textual descriptions and perceptions of the new systems.

Results: A total of 86 participants were recruited. The experimental arm achieved an 85.15% total correctness score, compared to 74.38% in the control arm (p < 0.001). The experimental arm particularly outperformed the control arm in the ambiguous tasks, such as compression low. However, despite a higher performance and greater agreement with the textual descriptions, the experimental group exhibited a less favourable perception compared to the control group.

Conclusion: Incorporating textual description into glucose monitoring systems enhances treatment decision-making for people with T1DM. It suggests that we are on the right path to helping them better understand their glucose data and assist their self-management. Extensive research is required to focus more on the patient-centred approach in information presentation and prioritise it in parallel with other advancements in glucose monitoring technologies.

Background: The impact of Graves' hyperthyroidism treatment on lipid metabolism remains unclear. This prospective observational study aimed to clarify the changes in lipid profiles and associated metabolic pathways, including cholesterol synthesis, absorption, and low-density lipoprotein (LDL) receptor regulation, following treatment.

Methods: Seventeen patients newly diagnosed with Graves' hyperthyroidism were enrolled and followed for 6 months after achieving euthyroid status. Serum lipids (total cholesterol, LDL-cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides), apolipoproteins, non-cholesterol sterols (markers of cholesterol synthesis and absorption), proprotein convertase subtilisin/kexin type 9 (PCSK9), and lipoprotein lipase (LPL) levels were measured at baseline, at euthyroid status (Eu-0M), and 6 months after euthyroid status (Eu-6M).

Results: After treatment, serum total cholesterol, LDL-C, and HDL-C levels increased rapidly compared to baseline, while triglyceride levels showed a delayed but significant increase at Eu-6M. Levels of apolipoprotein (apo) AI, AII, B, and CIII increased significantly after treatment, whereas apo B-48 increased only at Eu-6M, and apo CII and apo E remained unchanged. Markers of cholesterol synthesis (lathosterol) and absorption (sitosterol, campesterol, and cholestanol) increased significantly after treatment, indicating enhanced cholesterol metabolism. Circulating PCSK9 levels increased significantly and remained elevated, while LPL levels did not change significantly.

Conclusion: Treatment of Graves' hyperthyroidism rapidly increases cholesterol levels through enhanced cholesterol synthesis and absorption, possibly mediated by increased circulating PCSK9.

Cancer negatively impacts bone health through various mechanisms, including treatment-induced bone loss and malignant bone lesions, often leading to increased fracture risk and higher morbidity and mortality. Antiresorptive agents (bisphosphonates and denosumab) are the current standard of care to reduce the risk of skeletal-related events and prevent treatment-related fragility fractures in patients with cancer. While there is strong evidence to support their benefits in cancer, there is potential room for further reduction in the risk of pathologic and fragility fractures. This narrative review explores the potential role and theoretical concerns regarding the use of osteoanabolic agents in cancer. We also discuss management challenges, such as recurrent pathologic fractures, fragility fractures, and osteonecrosis of the jaw that may arise in clinical practice, prompting consideration of the use of osteoanabolic agents in patients with a history of cancer. Preclinical studies have shown conflicting outcomes regarding the effects on cancer with parathyroid hormone treatment, but promising results with the use of anti-sclerostin antibody in cancer models. Definitive conclusions cannot be drawn from available preclinical and clinical data. Theoretical risks exist for both cancer survivors and patients with advanced cancer in the bone. Therefore, the risk-benefit ratio should be carefully considered when evaluating the use of an osteoanabolic agent in the cancer context.

Background: Exercise-induced muscle soreness and fatigue are significant barriers to physical activity in middle-aged women with type 2 diabetes (T2D), exacerbated by impaired tissue healing and chronic inflammation.

Objectives: To evaluate whether post-exercise therapeutic ultrasound (TUS) effectively reduces exercise-induced muscle soreness and fatigue while improving metabolic and inflammatory biomarkers in women with T2D.

Design: Randomized controlled trial.

Methods: Thirty sedentary women with T2D (aged 41-49 years, glycated hemoglobin (HbA1c) 6.5%-9.0%) were randomized to a TUS group (n = 15) or control (n = 15). Both groups completed an 8-week aerobic cycling program (3 sessions/week, 45 min/session, 60%-70% VO₂max). The TUS group received post-exercise ultrasound (3 MHz, 1 W/cm², 7 min/leg) using the Intellect Mobile 2 device. Primary outcomes were pain (Von Korff scale) and fatigue (Borg scale), while secondary outcomes included fasting blood sugar (FBS), HbA1c, inflammatory markers (tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6)), and creatine kinase (CK), assessed at baseline and post-intervention. Linear mixed-effects models adjusted for baseline pain differences.

Results: The TUS group showed marked decreases in pain (-2.2, 95% CI: -2.8 to -1.6, p < 0.001) and fatigue (-1.8, 95% CI: -2.4 to -1.2, p = 0.004) compared to controls. Secondary outcomes substantially improved: HbA1c (-0.5%, p = 0.03), FBS (-19.8 mg/dL, p = 0.01), TNF-α (-24.9 pg/mL, p < 0.001), IL-6 (-11.9 pg/mL, p < 0.001), and CK (-30 U/L, p = 0.01). No adverse events were reported.

Conclusion: TUS is a safe, effective adjunct for reducing exercise-induced muscle soreness and fatigue in women with T2D, with benefits in glycemic control and inflammation. Larger trials with sham controls are needed.

Trial registration: This trial was registered at the Iranian Registry of Clinical Trials (IRCT20211201053244N1) on June 21, 2022.

Background: Chronic limb-threatening ischaemia (CLTI) causes high rates of amputation and mortality.

Objectives: To compare incidence, management and prognosis in hospitalised patients with CLTI with and without diabetes mellitus (DM) in 2001 and 2023. A secondary objective was to compare adherence to global vascular guidelines on risk factors between patients with and without DM in 2023.

Design: Retrospective study.

Methods: Group differences were tested using the Mann-Whitney U test, independent sample t test or the Chi-square test, as appropriate. The effects of DM on major amputation or mortality at 1 year were evaluated in a multivariable logistic regression model according to a directed acyclic graph.

Results: The incidence of hospitalisations for CLTI was reduced from 37.4 (95% confidence interval (CI), 33.3-41.6) in 2001 to 22.8 (95% CI, 19.7-25.8) per 100,000 person-years in 2023. The proportion of patients on full-dose oral anticoagulant therapy (p < 0.001) and lipid-lowering treatment (p < 0.001) increased significantly between the two time periods. In 2023, Wounds, Ischemia and foot Infection-classification in all patients with foot ulcers was documented in 6.9%. Anaemia was present at hospital admission in 67.0% and 52.5% of patients with CLTI with and without DM, respectively (p = 0.031). Endovascular therapy was performed more often in those with DM compared to those without DM (p = 0.004). Antiplatelet therapy (p = 0.008) and smoking cessation interventions (p = 0.033) were offered less often to those with DM. DM (odds ratio (OR), 1.7 (95% CI, 1.02-2.83)) was independently associated with increased mortality at 1 year, whereas period 2023 as opposed to 2001 (OR, 0.62 (95% CI, 0.38-0.99)) was associated with decreased mortality.

Conclusion: The incidence of hospitalisation for CLTI appears to have been reduced, and medical care of patients with CLTI has improved prognosis. Nevertheless, there is still room for large improvements of secondary prevention care in patients with CLTI, particularly in those with DM.