Therapeutic Advances in Endocrinology and Metabolism最新文献

Background: Type 2 diabetes mellitus is a growing epidemic condition that is expected to reach pandemic levels in the upcoming decades. Physical activity among individuals with type 2 diabetes is beneficial. A deeper understanding of physical activity among adults with type 2 diabetes in Jordan using a qualitative approach is needed.

Aim: This study aimed at exploring physical activity among adults with type 2 diabetes in Jordan.

Design: A constructivist grounded theory methodology guided this study.

Methods: Data were collected using semi-structured and audio-recorded interviews and then analysed simultaneously using coding, constant comparative analysis and writing reflexive memos.

Findings: Two themes emerged including 'The Perception about Physical Activity' and 'Factors Influencing Adherence to Physical Activity'. The first theme included four sub-themes: physical activity definition; importance; duration and types. The second theme included five sub-themes: the belief that diet is superior to physical activity; ageing and presence of diabetes or comorbidities; job and family obligations; social support and weather.

Conclusion: This study provided insights into patients' perceptions and adherence to physical activity including facilitators and barriers. Clinicians and policymakers may consider the findings of this study to develop health promotion programmes and to suggest a suitable environment for individuals with type 2 diabetes to enhance their physical activity.

• Children with growth hormone deficiency (GHD) are often prescribed a growth hormone called somatropin to help them grow. • As prescribed, somatropin needs to be injected once a day under the skin. Some children may miss many of their somatropin injections, and this is known as having "low adherence" to treatment. Adherence in this study refers to whether the children had enough somatropin to have daily injections as prescribed. • In this study, researchers found that children with GHD who had high adherence to daily somatropin injections grew more than children who had low adherence to daily somatropin injections. • Researchers, doctors, and nurses need to look at how they can help children with GHD follow their prescribed injection schedule and reduce the number of missed injections. The purpose of this plain language summary is to help you to understand the findings from recent research. • Somatropin is approved to treat the condition under study that is discussed in this summary. • This summary reports the results of a single study. The results of this study may differ from those of other studies. Health professionals should make treatment decisions based on all available evidence, not on the results of a single study. Glossary of commonly used terms Adherence - in this study, adherence refers to whether the children had enough medication (somatropin) to have daily injections as prescribed by their doctor. Growth hormone - a protein made in the pituitary gland that helps the body grow properly. Growth hormone deficiency - children with this condition do not have enough growth hormone in their bodies so they grow more slowly than children with normal levels of growth hormone. Somatropin - a type of human growth hormone that can be made in a laboratory and used to treat growth hormone deficiency.

Background: There is interest in repurposing bicalutamide for gender-affirming hormone therapy, but little data regarding efficacy and safety in the transgender population.

Objectives: To determine the effect of bicalutamide on serum total testosterone concentrations and liver function. Given bicalutamide is a pure androgen receptor antagonist, we hypothesized that serum total testosterone concentrations would be higher than the cisgender female reference range and those recommended for transgender individuals in consensus guidelines.

Design: Case series.

Methods: We identified transgender people attending outpatient clinics who were using bicalutamide for gender affirmation. The primary outcome was serum total testosterone concentration. Secondary outcomes included serum alanine transferase (ALT) concentration.

Results: Twenty-four transfeminine people prescribed bicalutamide were identified. The median (interquartile range) age was 29 (24-38) years, bicalutamide dose 25 (25-50) mg daily and bicalutamide duration 6 (4-10) months. The median serum total testosterone concentration was 7.7 (0.7-17.5) nmol/L, luteinizing hormone 2.9 (0.5-6.0) IU/L and ALT 20 (13-29) IU/L. One individual had asymptomatic transaminitis. Six individuals discontinued bicalutamide due to a lack of perceived benefit.

Conclusion: Bicalutamide was associated with significant variation in serum total testosterone concentration, likely related to concomitant estradiol or previous anti-androgen therapy. Median serum ALT concentrations remained within the normal reference range. Guideline recommendations for serum total testosterone within the cisgender female reference range may be inappropriate for people using bicalutamide. Further research is needed to establish the longer-term efficacy and safety of bicalutamide in the transfeminine population.

Ectopic corticotropin-releasing hormone (CRH) syndrome, a rare subtype of adrenocorticotropic hormone-dependent Cushing syndrome, is associated with tumors of diverse origins. Here, we present a case of a 37-year-old female diagnosed with ectopic CRH syndrome secondary to rectal large cell neuroendocrine carcinoma, a hitherto unprecedented site for CRH-secreting tumors. The patient presented with classical features of Cushing syndrome, supported by laboratory evidence of hypercortisolemia and disrupted diurnal cortisol secretion. Imaging studies ruled out a pituitary adenoma, whereas colonoscopy identified a rectal malignancy. Immunohistochemical staining confirmed the presence of ectopic CRH syndrome. Despite prompt chemotherapy initiation, the patient's condition rapidly deteriorated, highlighting the aggressive nature and dismal prognosis associated with rectal large cell neuroendocrine carcinoma linked to ectopic CRH syndrome. This case underscores the importance of early recognition and comprehensive management to optimize patient outcomes.

Background: Continuous glucose monitoring (CGM) with minimally invasive devices plays a key role in the assessment of daily diabetes management by detecting and alerting to potentially dangerous trends in glucose levels, improving quality of life, and treatment adherence. However, there is still uncertainty as to whether CGMs are accurate enough to replace self-monitoring of blood glucose, especially in detecting episodes of hypoglycemia.

Objectives: Evaluate clinical, numerical accuracy, sensitivity, and specificity of the CGM devices commercially available when compared to the reference standard of arterial or venous blood glucose.

Data sources and methods: We searched the Cochrane Library, PubMed, EMBASE, and LILACS databases. The quality was assessed with the Quality Assessment Diagnostic Accuracy Studies (QUADAS-2) tool. Clinical and numerical accuracy data were extracted. Sensitivity and specificity were calculated using Review Manager software. Heterogeneity was assessed by visual examination of forest plot and summary receiver operating characteristic curves.

Results: Twenty-two studies with a total of 2294 patients were included. The average mean absolute relative difference for overall diagnostic accuracy was 9.4%. None of the devices evaluated with ISO 15197:2013 criteria achieved values ⩾95% of measurements in the stipulated ranges in hypoglycemia (±15 mg/dL), but two devices did achieve it in hyperglycemia (±15%; Dexcom G6 and G7). Most of the devices evaluated with consensus error grids reached values above 99% in zones A and B only in overall accuracy and hyperglycemia. For hypoglycemia, the average sensitivity was 85.7% and specificity 95.33%, and for hyperglycemia was 97.45% and 96% respectively.

Conclusion: Currently available CGM devices have adequate accuracy for euglycemia and hyperglycemia; however, it is still inadequate for hypoglycemia, although it has improved over time.

Trial registration: Prospero registration ID CRD42023399767.

Background: Hyperglycemic emergencies (HGEs) are the major deadliest acute complications of diabetes. HGEs have reached an alarming stage and increased year-to-year leading to increased morbidity, hospitalization, and mortality. Despite HGEs causing this increased healthcare, psychological, social, and economic burden, studies conducted to address this burden and its predictive factors remain limited. Thus, this study aimed to investigate the incidence and predictors of HGEs among adult diabetic patients.

Methods: An institution-based retrospective follow-up study was employed on 538 systematically selected adult diabetic patients who had diabetic follow-up in Sidama region and Gedeo zone public hospitals from September 1, 2018, to September 1, 2022. The sample size was determined using STATA V-14. Data were collected using an extraction checklist, entered into EPI data version 4.4.2.2, and analyzed using STATA version 14. The Kaplan-Meier curve and log-rank test were used to determine the survival probabilities and to compare the survival status. The Cox proportional hazard regression model was used to determine the association and identify the predictor variables. A statistical significance was declared at a p-value of <0.05 in line with a 95% confidence interval (CI) and hazard ratios.

Results: The study was conducted on 538 diabetic adult patients with a response rate of 100%. The mean age of study participants was 44.5 years, and more than 66.7% were males. The incidence rate of HGEs was found to be 29 (95% CI: 25.3-33.2) per 1000 person-months with a total of 7176.5 person-month observations. Being farmer (adjusted hazard ratio (AHR) = 6.47; 95% CI: 2.61-16.04), poor glycemic control (AHR = 6.84; 95% CI: 3.47-13.49), less frequent diabetic follow-up (AHR = 4.00; 95% CI: 1.02-15.57), and having hypertension (HTN) (AHR = 2.94; 95% CI: 1.62-5.34) were significantly associated with increased hazard of acquiring HGEs among adult diabetic patients. Conversely, the hazard of experiencing HGE was 63% lower among patients who had diabetic nephropathy relative to those without diabetic nephropathy (AHR = 0.35; 95% CI: 0.15-0.83). Hence, setting and strengthening specific diabetic management strategies focused on the identified predictors could be paramount to reducing HGEs and their unwanted effects. Moreover, it's better to consider more frequent diabetic follow-up visits for all patients regardless of other complications.

Background: The aldosterone-to-renin ratio (ARR) is commonly used for screening primary aldosteronism (PA) in patients with difficult-to-control hypertension. Various thresholds have been proposed for the confirmatory tests, leading to inconsistency in the results.

Objectives: This study aimed to elucidate the performance of ARR screening in hypertensive patients.

Design: Systemic review and meta-analysis.

Data sources and methods: PubMed, Embase, and the Cochrane Library were systematically searched from inception to January 2024. Studies that used the ARR to screen for PA and provided a comprehensive probability panel specifically focusing on hypertensive individuals were considered for enrollment. Pooled diagnostic efficacy was evaluated, and subgroup analyses and meta-regression were conducted based on different demographic and clinical parameters.

Results: Eighteen observational studies encompassing 7150 participants were included in the meta-analysis. The overall prevalence of PA in the hypertensive cohort was 15.2%, and pooled sensitivity and specificity were 81.6% and 93.3%, respectively, resulting in a diagnostic odds ratio of 62.0. Fagan's nomogram showed that a positive ARR increased the post-test probability to 80% from a pre-test probability of 25%. Summary receiver operating characteristic curve analysis revealed an area under the curve of 94.7%. Notably, analysis of variability demonstrated that the diagnostic performance was consistent across either ARR based on plasma renin activity or direct renin concentration, geographic region, sex, mean age, potassium level, and systolic blood pressure.

Conclusion: ARR was validated as a viable screening methodology for PA in hypertensive individuals. Moreover, its diagnostic efficacy remained unchanged across diverse clinical contexts. Future studies are warranted to refine ARR methodologies and enhance diagnostic accuracy.

Trial registration: PROSPERO ID number CRD42023493680.

Infographics: Performance of PA screening by ARR. ARR, aldosterone-to-renin ratio; BP, blood pressure; DRC, direct renin concentration; hsROC, hierarchical summary receiver operating characteristic; PA, primary aldosteronism; PRA, plasma renin activity.

Background: There is limited data about the risk factors of clinically significant glycosylated hemoglobin (HbA1c) change and post-transplant diabetes mellitus (PTDM) in the first year post-kidney transplantation (KT), especially in the Middle East.

Objectives: To determine the trends of HbA1c levels, the risk factors associated with HbA1c increases, and predictors of clinically significant HbA1c change and PTDM in the first year post-KT.

Design: Retrospective chart review.

Methods: We included all KT recipients (KTRs) at our center from 2017 until 2020. The study focused on reviewing the patients' demographic information, cardiovascular risk factors, and HbA1c values at baseline, 6 months, and 12 months.

Results: A total of 203 KTRs were included. The mean age of the participants was 44.7 ± 15.5 years, 59.1% were men, and 80.3% received living donors. Eighty-two (40.4%) KTRs had pre-KT diabetes. At 12 months post-KT, the total HbA1c change was 0.87 ± 1.6. In total, 130 (64.04%) KTRs demonstrated clinically significant HbA1c change, and 19 (15.7%) nondiabetics developed PTDM. Pre-KT diabetics suffered greater increases than their nondiabetic counterparts (0.8 vs 0.6, p = 0.043). Increased age (adjusted odds ratio (aOR) = 1.053), weight change (aOR = 1.055), pre-KT hypertension (aOR = 3.015), and lower baseline HbA1c (aOR = 0.453) were independently associated with clinically significant HbA1c change. PTDM patients were older (p = 0.007) and had higher HbA1c levels at baseline (p = 0.033), 6 months (p = 0.002), and 1-year post-KT (p = 0.001). Gender, type of KT, dialysis, and cardiovascular risk factors were not different between PTDM and non-PTDM patients. Abnormal perfusion tests (p < 0.001) and coronary artery disease on coronary angiogram (p = 0.046) were more common in PTDM patients. Only age was independently associated with the presence of PTDM at 1-year post-KT (aOR = 1.044).

Conclusion: The incidence rate of PTDM in Saudi KT patients is similar to that of other populations. Several risk factors, including low baseline HbA1c and pre-KT hypertension, predict a clinically significant change in HbA1c. Patients with these risk factors may require stricter monitoring and control of HbA1c.

• The efficacy of weekly somatrogon injections was no different from that of daily somatropin injections to treat children who don't make enough growth hormone to grow adequately. ○ Efficacy refers to how well a drug works in a clinical trial. ○ Children treated with weekly somatrogon had an increased growth rate, similar to that of children treated with daily somatropin. • The safety of weekly somatrogon injections was similar to that of daily somatropin injections. The original scientific article on which this summary is based was published in The Journal of Clinical Endocrinology & Metabolism and can be accessed for free at: https://academic.oup.com/jcem/article/107/7/e2717/6566444. The details of the original article are as follows: Cheri L. Deal, Joel Steelman, Elpis Vlachopapadopoulou, Renata Stawerska, Lawrence A Silverman, Moshe Phillip, Ho-Seong Kim, CheolWoo Ko, Oleg Malievskiy, Jose F. Cara, Carl L. Roland, Carrie Turich Taylor, Srinivas Rao Valluri, Michael P. Wajnrajch, Aleksandra Pastrak, and Bradley S. Miller. Efficacy and safety of weekly somatrogon vs daily somatropin in children with growth hormone deficiency: a phase 3 study. J Clin Endocrinol Metab 2022; 107(7): e2717-e2728. The purpose of this plain language summary is to help you to understand the findings from recent research. • Somatrogon is used to treat growth hormone deficiency (the condition under study that is 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. Physicians/providers should make treatment decisions based on all available evidence and not on the results of a single study.

Background: Diabetic foot ulcer (DFU) is a common and highly morbid complication of diabetes with high unmet medical needs. AUP1602-C, a topical four-in-one gene therapy medicinal product (GTMP), consisting of a Lactococcus cremoris strain that produces fibroblast growth factor-2, interleukin-4, and colony-stimulating factor-1, is a promising novel treatment for DFU.

Objectives: The aim of this first-in-human study was to investigate whether AUP1602-C is safe and effective in improving wound healing and quality of life (QoL) in patients with non-healing DFU (nhDFU), and to determine the recommended phase II dose.

Design: Phase I, single-arm, open-label, uncontrolled, dose escalation study.

Methods: The study consisted of four cohorts of patients receiving AUP1602-C as a single dose of 2.5 × 10⁵ colony-forming units (CFU)/cm² ulcer size or as repeated doses between 2.5 × 10⁶ and 2.5 × 10⁸ CFU/cm² administered 3 times per week for 6 weeks. Within each cohort, a 3 + 3 scheme for monitoring safety, tolerability, and efficacy was applied.

Results: In total, 16 patients aged 53-80 years were included, 3 each in the safety and low dose, 4 in the medium dose, and 6 in the high-dose cohort. AUP1602-C demonstrated a favorable safety profile with almost 100% dosing compliance. The most frequently reported side effect related to treatment was skin maceration. No serious adverse reactions, systemic toxicity, deaths, or side effects suggestive of immunogenicity, hypersensitivity, allergic reaction, or dose-limiting toxicities related to treatment were reported. No biodistribution events were observed and shedding-related events were rare and did neither show accumulation nor dose dependency. The recommended phase II dose of 2.5 × 10⁸ CFU/cm² demonstrated complete healing in 83% of patients without recurrence of ulcers during follow-up.

Conclusion: AUP1602-C was safe and well tolerated and demonstrated dose-dependent efficacy in patients with nhDFU. Data supports further clinical development of AUP1602-C.

Trial registration: The study was registered in ClinicalTrials.gov (NCT04281992) and ClinicalTrialsRegister.eu (2018-003415-22).