Therapeutic Advances in Endocrinology and Metabolism最新文献

{"title":"Semaglutide in the spotlight: weighing benefits against rising concerns.","authors":"Patrick Ashinze, Toufik Abdul-Rahman, Andrew Awuah Wireko","doi":"10.1177/20420188231222394","DOIUrl":"10.1177/20420188231222394","url":null,"abstract":"","PeriodicalId":22998,"journal":{"name":"Therapeutic Advances in Endocrinology and Metabolism","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10768618/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139378306","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dual-basal-insulin regimen for the management of dawn phenomenon in children with type 1 diabetes: a retrospective cohort study.","authors":"Nur Berna Celik, Dicle Canoruc Emet, Merve Canturk, Z Alev Ozon, E Nazli Gonc","doi":"10.1177/20420188231220130","DOIUrl":"10.1177/20420188231220130","url":null,"abstract":"<p><strong>Background: </strong>Handling of the dawn phenomenon (DP) with multiple daily insulin injection (MDII) regimen is a real challenge.</p><p><strong>Objective: </strong>We aimed to demonstrate the effectiveness of a dual-basal-insulin (a long-acting glargine and an intermediate-acting neutral protamine Hagedorn (NPH)) regimen for the management of DP in children with type 1 diabetes mellitus (T1DM). The primary efficacy outcome was to overcome morning hyperglycemia without causing hypoglycemia during the non-DP period of the night.</p><p><strong>Design: </strong>Retrospective cohort study.</p><p><strong>Method: </strong>Charts of 28 children with T1DM (12 female; 42.8%, mean age 13.7 ± 2.1 years) treated with MDII were retrospectively reviewed. The median duration of diabetes was 4.5 years (range 2-13.5 years). DP was diagnosed using a threshold difference of 20 mg/dL (0.1 mmol/L) between fasting capillary blood glucose at 3 a.m. and prebreakfast. NPH was administered at midnight in addition to daily bedtime (08.00-09.00 p.m.) glargine (dual-basal-insulin regimen). Midnight, 03:00 a.m., prebreakfast and postprandial capillary blood glucose readings, insulin-carbohydrate ratios, and basal-bolus insulin doses were recorded the day before the dual-basal-insulin regimen was started and the day after the titration of the insulin doses was complete. Body mass index standard deviation scores (BMI SDS) at the onset-3rd-12th month of treatment were noted.</p><p><strong>Results: </strong>Before using dual basal insulin, prebreakfast capillary blood glucose levels were greater than those at midnight and at 03:00 a.m. (<i>F</i> = 64.985, <i>p</i> < 0.01). After titration of the dual-basal-insulin doses, there were significant improvements such that there were no statistically significant differences in the capillary blood glucose measurements at the three crucial time points (midnight, 03.00 a.m., and prebreakfast; <i>F</i> = 1.827, <i>p</i> = 0.172). No instances of hypoglycemia were reported, and the total daily insulin per kilogram of body weight did not change. The BMI SDS remained steady over the course of the 1-year follow-up.</p><p><strong>Conclusion: </strong>In this retrospective cohort study, the dual-basal-insulin regimen, using a long-acting glargine and an intermediate-acting NPH, was effective in overcoming early morning hyperglycemia due to insulin resistance in the DP. However, the effectiveness of the dual-basal-insulin regimen needs to be verified by prospective controlled studies using continuous glucose monitoring metrics or frequent blood glucose monitoring.</p>","PeriodicalId":22998,"journal":{"name":"Therapeutic Advances in Endocrinology and Metabolism","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2023-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10752105/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139049346","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessing the prediction of type 2 diabetes risk using polygenic and clinical risk scores in South Asian study populations.","authors":"Madhusmita Rout, Gurpreet S Wander, Sarju Ralhan, Jai Rup Singh, Christopher E Aston, Piers R Blackett, Steven Chernausek, Dharambir K Sanghera","doi":"10.1177/20420188231220120","DOIUrl":"10.1177/20420188231220120","url":null,"abstract":"<p><strong>Background: </strong>Genome-wide polygenic risk scores (PRS) have shown high specificity and sensitivity in predicting type 2 diabetes (T2D) risk in Europeans. However, the PRS-driven information and its clinical significance in non-Europeans are underrepresented. We examined the predictive efficacy and transferability of PRS models using variant information derived from genome-wide studies of Asian Indians (AIs) (PRS_AI) and Europeans (PRS_EU) using 13,974 AI individuals.</p><p><strong>Methods: </strong>Weighted PRS models were constructed and analyzed on 4602 individuals from the Asian Indian Diabetes Heart Study/Sikh Diabetes Study (AIDHS/SDS) as discovery/training and test/validation datasets. The results were further replicated in 9372 South Asian individuals from UK Biobank (UKBB). We also assessed the performance of each PRS model by combining data of the clinical risk score (CRS).</p><p><strong>Results: </strong>Both genetic models (PRS_AI and PRS_EU) successfully predicted the T2D risk. However, the PRS_AI revealed 13.2% odds ratio (OR) 1.80 [95% confidence interval (CI) 1.63-1.97; <i>p</i> = 1.6 × 10^-152] and 12.2% OR 1.38 (95% CI 1.30-1.46; <i>p</i> = 7.1 × 10^-237) superior performance in AIDHS/SDS and UKBB validation sets, respectively. Comparing individuals of extreme PRS (ninth decile) with the average PRS (fifth decile), PRS_AI showed about two-fold OR 20.73 (95% CI 10.27-41.83; <i>p</i> = 2.7 × 10^-17) and 1.4-fold OR 3.19 (95% CI 2.51-4.06; <i>p</i> = 4.8 × 10^-21) higher predictability to identify subgroups with higher genetic risk than the PRS_EU. Combining PRS and CRS improved the area under the curve from 0.74 to 0.79 in PRS_AI and 0.72 to 0.75 in PRS_EU.</p><p><strong>Conclusion: </strong>Our data suggest the need for extending genetic and clinical studies in varied ethnic groups to exploit the full clinical potential of PRS as a risk prediction tool in diverse study populations.</p>","PeriodicalId":22998,"journal":{"name":"Therapeutic Advances in Endocrinology and Metabolism","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2023-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10752110/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139049345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hippo/YAP signaling pathway: a new therapeutic target for diabetes mellitus and vascular complications.","authors":"Lan Wei, Jingjing Gao, Liangzhi Wang, Qianru Tao, Chao Tu","doi":"10.1177/20420188231220134","DOIUrl":"10.1177/20420188231220134","url":null,"abstract":"<p><p>Diabetic angiopathy, which includes diabetic kidney disease (DKD), cardio-cerebrovascular disease, and diabetic retinopathy (DR) among other diseases, is one of the most common complications affecting diabetic patients. Among these, DKD, which is a major cause of morbidity and mortality, affects about 40% of diabetic patients. Similarly, DR involves retinal neovascularization and neurodegeneration as a result of chronic hyperglycemia and is the main cause of visual impairment and blindness. In addition, inflammation also promotes atherosclerosis and diabetes, with atherosclerosis-related cardiovascular diseases being often a main cause of disability or death in diabetic patients. Given that vascular diseases caused by diabetes negatively impact human health, it is therefore important to identify appropriate treatments. In this context, some studies have found that the Hippo/Yes-associated protein (YAP) pathway is a highly evolutionarily conserved protein kinase signal pathway that regulates organ growth and size through its effector signaling pathway Transcriptional co-Activator with PDZ-binding motif (TAZ) and its YAP. YAP is a key factor in the Hippo pathway. The activation of YAP regulates gluconeogenesis, thereby regulating glucose tolerance levels; silencing the YAP gene thereby prevents the formation of glomerular fibrosis. YAP can combine with TEA domain family members to regulate the proliferation and migration of retinal vascular endothelial cells (ECs), so YAP plays a prominent role in the formation and pathology of retinal vessels. In addition, YAP/TAZ activation and translocation to the nucleus promote endothelial inflammation and monocyte-EC attachment, which can increase diabetes-induced cardiovascular atherosclerosis. Hippo/YAP signaling pathway provides a potential therapeutic target for diabetic angiopathy, which can prevent the progression of diabetes to DR and improve renal fibrosis and cardio-vascular atherosclerosis.</p>","PeriodicalId":22998,"journal":{"name":"Therapeutic Advances in Endocrinology and Metabolism","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2023-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10752099/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139049347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Zoledronic acid sequential to teriparatide may promote greater inhibition of bone resorption than zoledronic acid alone.","authors":"Sharon Giveon, Galia Zacay, Iris Vered, A Joseph Foldes, Liana Tripto-Shkolnik","doi":"10.1177/20420188231213639","DOIUrl":"https://doi.org/10.1177/20420188231213639","url":null,"abstract":"<p><strong>Background: </strong>Teriparatide (TPTD) should be followed by an antiresorptive to maximize bone mineral density gain and anti-fracture protection. Infrequent zoledronic acid (ZOL) administration has demonstrated effectiveness. The duration of ZOL effect following TPTD is unknown.</p><p><strong>Objective: </strong>To evaluate the effect of ZOL on bone resorption marker in a post-TPTD <i>versus</i> ZOL-alone scenario in osteoporotic patients.</p><p><strong>Design: </strong>Retrospective cohort study.</p><p><strong>Methods: </strong>Patients treated with TPTD followed by ZOL (TPTD-ZOL) or with a single ZOL infusion were identified in the database of a tertiary referral center. Clinical and laboratory data, including C-terminal telopeptide of type I collagen (CTX) following ZOL treatment, were compared.</p><p><strong>Results: </strong>Twenty-six patients (93% women) treated with TPTD-ZOL and 41 with ZOL were comparable in age (median 70.1 <i>versus</i> 69.6 years, <i>p</i> = 0.6) and sex. Timing of CTX measurement post-ZOL was the same, median 1.0 year. CTX was lower following TPTD-ZOL (median 142.1 <i>versus</i> 184.2 pg/mL, <i>p</i> = 0.005). In a multivariable regression model (controlled for baseline characteristics), pretreatment with TPTD strongly predicted CTX <150 pg/mL, 1 year following ZOL (odds ratio = 7.5, 95% CI 1.3-58.1, <i>p</i> = 0.03). In a subgroup with sequential CTX measurements following one ZOL, significantly lower levels persisted in the TPTD-ZOL group for a median of 4.4 years follow-up.</p><p><strong>Conclusion: </strong>ZOL-administered sequential to TPTD yielded deeper and more prolonged bone resorption suppression than ZOL alone. Prospective data are needed to confirm whether in a sequential treatment scenario, subsequent ZOL dosing interval should be less frequent.</p>","PeriodicalId":22998,"journal":{"name":"Therapeutic Advances in Endocrinology and Metabolism","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2023-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10666713/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138462777","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hypovitaminosis D masking hypercalcemia in primary hyperparathyroidism: case report.","authors":"Tamer Mohamed Elsherbiny","doi":"10.1177/20420188231213208","DOIUrl":"https://doi.org/10.1177/20420188231213208","url":null,"abstract":"<p><p>Hyperparathyroidism (HPTH) is the third most common endocrine disorder. Hypovitaminosis D affects up to 40% of the general population and about a third of hyperparathyroid patients. Such a combination may alter the classic presentation of HPTH. This report presents a premenopausal female with long history of osteoporosis, normocalcemia, and hypovitaminosis D who was initially diagnosed as secondary HPTH. After restoring vitamin D to normal using parenteral loading doses, the patient developed persistent mild to moderate hypercalcemia with persistent parathormone elevation consistent with primary HPTH associated with hypercalciuria and complicated with nephrocalcinosis. Imaging confirmed a left upper parathyroid adenoma and fulfilling several indications for surgery, the patient was operated restoring normocalcemia that was maintained for several years of follow-up. Hypovitaminosis D is common and may mask expected hypercalcemia in patients with primary HPTH, thus delaying diagnosis and proper intervention. Reevaluating patients initially diagnosed as hypovitaminosis D and secondary HPTH may reveal a masked diagnosis of primary hyperparathyroidism.</p>","PeriodicalId":22998,"journal":{"name":"Therapeutic Advances in Endocrinology and Metabolism","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2023-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10656797/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138462776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Design and rationale for the SIB trial: a randomized parallel comparison of semaglutide <i>versus</i> placebo on intestinal barrier function in type 2 diabetes mellitus.","authors":"Steven Rella,&nbsp;Joseph Onyiah,&nbsp;Chelsea Baker,&nbsp;Vatsala Singh,&nbsp;Andrew Her,&nbsp;Neda Rasouli","doi":"10.1177/20420188231207348","DOIUrl":"https://doi.org/10.1177/20420188231207348","url":null,"abstract":"<p><strong>Objective: </strong>To describe the rationale and design of the SIB trial, an interventional clinical trial testing the hypothesis that subcutaneous (s.c.) once-weekly semaglutide can improve intestinal permeability and reduce systemic inflammation in participants with type 2 diabetes (T2D) and obesity.</p><p><strong>Methods: </strong>SIB (NCT04979130) is an investigator-initiated, single-center randomized, double-blinded, placebo-controlled clinical study being conducted at the University of Colorado Anschutz Medical Campus. The primary objective of this novel trial is to test the hypothesis that subcutaneous (s.c.) once-weekly semaglutide could improve intestinal permeability and reduce systemic inflammation in participants with T2D and obesity. Eligible participants had a diagnosis of type 2 diabetes, elevated body mass index, and evidence of systemic inflammation. Participants were randomized 1:1 to s.c. semaglutide or placebo. Participants were assessed for intestinal permeability and markers of inflammation at baseline, mid-study, and at the end of the study. Efficacy assessments were based on the analysis of the following: lactulose:mannitol ratio test, serum lipopolysaccharide-binding protein (LBP), fecal calprotectin, inflammatory biomarkers (IL-6, TNF, IL-1, IL-8, hs-CRP), and HbA1c. All participants who enrolled in the trial provided written informed consent after having received written and oral information on the trial. The risks of semaglutide use were minimized by administration according to FDA-labeled use and close monitoring for adverse events.</p><p><strong>Discussion: </strong>SIB is the first study to examine the effects of GLP-1 receptor agonists on intestinal permeability in humans and will provide important data on their impact on systemic inflammation and intestinal permeability in the setting of T2D and obesity.</p>","PeriodicalId":22998,"journal":{"name":"Therapeutic Advances in Endocrinology and Metabolism","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2023-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10617296/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71427151","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Soluble tumor necrosis factor receptor type 1 predicts cardiorenal outcomes and better associated with distinct cardiovascular or renal outcomes than precedential renal or cardiovascular events in type 2 diabetes mellitus.","authors":"Li-Hsin Chang,&nbsp;Chia-Huei Chu,&nbsp;Chin-Chou Huang,&nbsp;Liang-Yu Lin","doi":"10.1177/20420188231207345","DOIUrl":"https://doi.org/10.1177/20420188231207345","url":null,"abstract":"<p><strong>Background: </strong>Inflammations are the crucial pathogenesis of chronic complications of type 2 diabetes mellitus (T2DM).</p><p><strong>Objectives: </strong>The timeline of cardiovascular and renal complications of T2DM and whether soluble tumor necrosis factor receptor type 1 (sTNFR1) levels predict cardiorenal outcomes were still elusive.</p><p><strong>Design: </strong>Prospectively observational study.</p><p><strong>Methods: </strong>Chinese patients with T2DM were enrolled. Cardiorenal composite events defined by either cardiovascular composite events (all-cause mortality, acute coronary syndrome, or non-fatal stroke) or renal composite events (a decline of >30% of renal function or worsening status of albuminuria) were followed. Associations of sTNFR1 levels and cardiovascular, renal, and cardiorenal composite events were analyzed in regression models presented by hazard ratio (HR) and 95% confidence interval (95% CI).</p><p><strong>Results: </strong>Among 370 subjects, 42 cardiovascular and 86 renal composite events occurred. Higher sTNFR1 levels were related to higher frequency and risks of cardiovascular composite events (HR 1.07, 95% CI 1.01-1.13, <i>p</i> = 0.009) and renal composite events (HR 1.05, 95% CI 1.02-1.09, <i>p</i> < 0.001). Occurrences of cardiovascular composite events were not predicted by precedential renal composite events. sTNFR1 levels were proved to be associated with risks of cardiorenal composite events in Cox regression sequential models (adjusted HR 1.04, 95% CI 1.00-1.08, <i>p</i> = 0.03). The results were consistent in all subgroup analyses.</p><p><strong>Conclusion: </strong>Levels of sTNFR1 were associated with cardiorenal complications of T2DM and the predictabilities of TNFR1 levels were better than precedential cardiovascular or renal events.</p>","PeriodicalId":22998,"journal":{"name":"Therapeutic Advances in Endocrinology and Metabolism","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2023-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10617259/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71427153","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pheochromocytoma: a changing perspective and current concepts.","authors":"Andreas Kiriakopoulos,&nbsp;Periklis Giannakis,&nbsp;Evangelos Menenakos","doi":"10.1177/20420188231207544","DOIUrl":"https://doi.org/10.1177/20420188231207544","url":null,"abstract":"<p><p>This article aims to review current concepts in diagnosing and managing pheochromocytoma and paraganglioma (PPGL). Personalized genetic testing is vital, as 40-60% of tumors are linked to a known mutation. Tumor DNA should be sampled first. Next-generation sequencing is the best and most cost-effective choice and also helps with the expansion of current knowledge. Recent advancements have also led to the increased incorporation of regulatory RNA, metabolome markers, and the NETest in PPGL workup. PPGL presentation is highly volatile and nonspecific due to its multifactorial etiology. Symptoms mainly derive from catecholamine (CMN) excess or mass effect, primarily affecting the cardiovascular system. However, paroxysmal nature, hypertension, and the classic triad are no longer perceived as telltale signs. Identifying high-risk subjects and diagnosing patients at the correct time by using appropriate personalized methods are essential. Free plasma/urine catecholamine metabolites must be first-line examinations using liquid chromatography with tandem mass spectrometry as the gold standard analytical method. Reference intervals should be personalized according to demographics and comorbidity. The same applies to result interpretation. Threefold increase from the upper limit is highly suggestive of PPGL. Computed tomography (CT) is preferred for pheochromocytoma due to better cost-effectiveness and spatial resolution. Unenhanced attenuation of >10HU in non-contrast CT is indicative. The choice of extra-adrenal tumor imaging is based on location. Functional imaging with positron emission tomography/computed tomography and radionuclide administration improves diagnostic accuracy, especially in extra-adrenal/malignant or familial cases. Surgery is the mainstay treatment when feasible. Preoperative α-adrenergic blockade reduces surgical morbidity. Aggressive metastatic PPGL benefits from systemic chemotherapy, while milder cases can be managed with radionuclides. Short-term postoperative follow-up evaluates the adequacy of resection. Long-term follow-up assesses the risk of recurrence or metastasis. Asymptomatic carriers and their families can benefit from surveillance, with intervals depending on the specific gene mutation. Trials primarily focusing on targeted therapy and radionuclides are currently active. A multidisciplinary approach, correct timing, and personalization are key for successful PPGL management.</p>","PeriodicalId":22998,"journal":{"name":"Therapeutic Advances in Endocrinology and Metabolism","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2023-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10617285/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71427152","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy of zoledronate, denosumab or teriparatide in postmenopausal women with type 2 diabetes mellitus at high risk of fragility fractures: protocol of an open, blinded endpoint randomized controlled pilot trial.","authors":"Trupti Nagendra Prasad,&nbsp;Sanjay Kumar Bhadada,&nbsp;Veenu Singla,&nbsp;Neelam Aggarwal,&nbsp;Sant Ram,&nbsp;Uttam Chand Saini,&nbsp;Ashok Kumar,&nbsp;Rimesh Pal","doi":"10.1177/20420188231207516","DOIUrl":"10.1177/20420188231207516","url":null,"abstract":"<p><strong>Background: </strong>People with type 2 diabetes (T2D) are at high risk of fragility fractures; however, there are no randomized controlled trials evaluating the efficacy of anti-osteoporosis drugs as a primary pre-specified endpoint in T2D.</p><p><strong>Objectives: </strong>To compare the efficacy of anti-osteoporotic drugs in postmenopausal women with T2D.</p><p><strong>Design: </strong>Prospective, randomized, open, blinded endpoint clinical pilot trial.</p><p><strong>Methods: </strong>Postmenopausal women (⩾50 years) with T2D (duration ⩾5 years), HbA1c 7-10%, eGFR ⩾45 mL/min/1.73 m² and prior vertebral (clinical/morphometric), hip, radius, humeral fragility fracture <i>or</i> bone mineral density (BMD) T-score (adjusted for diabetes) at lumbar spine/femoral neck ⩽-2.5 <i>and</i> high FRAX score will be eligible for inclusion. Subjects with secondary causes of osteoporosis, prior exposure to bone-active therapies or history of use of glucocorticoids/pioglitazone/thiazides/canagliflozin will be excluded. Finally, eligible subjects will undergo estimation of serum calcium, phosphate, alkaline phosphatase, parathyroid hormone, 25-hydroxyvitamin D and bone turnover markers (BTMs) (total procollagen type I N-propeptide, β-CTX) along with trabecular bone score (TBS) and high-resolution peripheral quantitative computed tomography (HR-pQCT) of non-dominant hand and leg. After a 2-week run in phase, they will be randomized in a 1:1:1:1 ratio to receive yearly zoledronate, or biannually denosumab or daily teriparatide (in addition to standard of care, i.e., calcium 1000 mg/day and cholecalciferol 1000 IU/day) or only standard of care (control). The primary endpoints will be change in areal BMD and frequency of incident fractures at 18 months. The secondary endpoints will be change in HR-pQCT parameters, TBS and BTMs at 18 months. Adverse events will be recorded for all randomized participants.</p><p><strong>Ethics: </strong>The study has been approved by the Institute Ethics Committee. Written informed consent will be obtained from each participant.</p><p><strong>Discussion: </strong>The trial is expected to provide information regarding optimal anti-osteoporotic therapy in people with T2D and bone fragility.</p><p><strong>Registration: </strong>Prospectively registered in Clinical Trial Registry of India (CTRI/2022/02/039978).</p>","PeriodicalId":22998,"journal":{"name":"Therapeutic Advances in Endocrinology and Metabolism","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2023-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/85/ae/10.1177_20420188231207516.PMC10590540.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49692521","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}