Journal of Clinical and Translational Endocrinology最新文献

{"title":"Identification of novel and recurrent mutations in nicotinamide nucleotide transhydrogenase (NNT) underlying familial glucocorticoid deficiency-type 4 in multiple Saudi families","authors":"Ibrahim Al Alwan ,&nbsp;Raja Hussain Ali ,&nbsp;Muhammad Umair ,&nbsp;Imran Ali Khan ,&nbsp;Nada Alotaibi ,&nbsp;Essra Aloyouni ,&nbsp;Deemah Alwadaani ,&nbsp;Latifah Alayyar ,&nbsp;Shahad Haddad ,&nbsp;Shahad Alawaji ,&nbsp;Saleh Althenayyan ,&nbsp;Ahmed Alfaidi ,&nbsp;Manal Algattan ,&nbsp;Ali S. Alquraishi ,&nbsp;Abdullah Alzaben ,&nbsp;Haifa Alfaraidi ,&nbsp;Beshaier Almulhem ,&nbsp;Mohammed Almannai ,&nbsp;Majid Alfadhel","doi":"10.1016/j.jcte.2026.100433","DOIUrl":"10.1016/j.jcte.2026.100433","url":null,"abstract":"<div><h3>Background</h3><div>Familial glucocorticoid deficiency (FGD; MIM: 614736) is a genetic disease of glucocorticoid insufficiency, with autosomal recessive mode of inheritance. The FGD is genetically heterogeneous disorder that involves multiple genes related to the pathway that regulates the signaling from pituitary to the adrenal cortex, or the specific redox reactions in mitochondria. The phenotypic spectrum for FGD is also diverse with considerable variability in clinical features. Among the genetic determinants of this disease, pathogenic mutations in <em>NNT</em> gene results in Familial glucocorticoid deficiency type 4. Here we report three consanguineous families with single nucleotide variants in <em>NNT</em> that manifest as familial glucocorticoid deficiency in multiple family members.</div></div><div><h3>Method</h3><div>Prospective cohort of three families from different tribes were identified with clinical diagnosis of familial glucocorticoid deficiency (FGD). Whole exome sequencing (WES) done for affected family members followed by validation of discovered variant by Sanger sequencing and subsequent functional studies including quantitative PCR analysis and protein Modelling.</div></div><div><h3>Results</h3><div>The screening of entire coding region of the genomes of probands in each family revealed three distinct mutations, including one novel missense variant (c.1067 C &gt; T; p.Thr356Ile), classified as variant of uncertain significance (VUS; Class-3) and two recurrent variants (c.1025 T &gt; C; p.Val342Ala and c.98dup; p.Leu33Phefs*13), classified as pathogenic [Class-I]. Computational protein modelling of these mutations (c.98dup and c.1025 T &gt; C) suggests atypical changes in the structure of the mutant proteins that likely disrupt the physiological role of NNT in mitochondria of adrenal cortex.</div></div><div><h3>Conclusion</h3><div>The exome sequencing genetically characterized the autosomal recessive sub-type 4 of hereditary glucocorticoid deficiency in families showing the features of cortisol deficiency, including the development of hypoglycemia and adrenal crisis. This strongly supports the pathogenicity of these variants. In addition, this suggests importance of mitochondrial function in post developmental maintenance of cortisol significance in terms of cellular metabolism, carried out by NNT protein. Identifying individuals with hereditary glucocorticoid deficiency is essential to start life-saving glucocorticoid replacement.</div></div>","PeriodicalId":46328,"journal":{"name":"Journal of Clinical and Translational Endocrinology","volume":"43 ","pages":"Article 100433"},"PeriodicalIF":3.3,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146173241","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Continuous glucose monitoring reveals high prevalence of hyperglycaemia in patients prior to pancreatic surgery: A pilot study","authors":"Heleen Driessens ,&nbsp;Josephine A.C. Woldring ,&nbsp;Maarten W. Nijkamp ,&nbsp;Peter R. van Dijk ,&nbsp;Joost M. Klaase","doi":"10.1016/j.jcte.2025.100426","DOIUrl":"10.1016/j.jcte.2025.100426","url":null,"abstract":"<div><h3>Aims</h3><div>Patients with pancreatic tumours are at increased risk of diabetes mellitus (DM) and hyperglycaemia and a subsequent higher risk of developing postoperative complications. Continuous glucose monitoring (CGM) can be used to assess the prevalence of hyperglycaemia in pancreatic surgery patients.</div></div><div><h3>Methods</h3><div>This single-centre observational pilot study (2023–2025) included 15 patients with DM type 2 or new onset DM (HbA1c ≥ 48 mmol/mol (6.5 %)) undergoing pancreatic surgery. Blinded CGM was performed for 2 weeks preoperatively and 2 weeks perioperatively. Primary outcome was time above range (TAR)(glucose &gt; 10.0 mmol/l (180.2 mg/dl)) as a percentage of total CGM wear time. Secondary outcomes were time below and in range, glucose metrics, difference in preoperative HbA1c and patient satisfaction regarding CGM wear.</div></div><div><h3>Results</h3><div>In total, 5 patients had new-onset DM, 6 suboptimal controlled DM (HbA1c ≥ 53 mmol/mol (7.0 %)) and 4 optimal controlled DM (HbA1c &lt; 53 mmol/mol (7.0 %)) at baseline. Median preoperative TAR (&gt;10.0 mmol/L (180.2 mg/dl)) was highest in the suboptimal controlled DM group (59.7 % [35.1–68.6]), compared to 7.9 % [0.9–19.4] in the optimal controlled and 16.7 % [7.7–23.7] in the new-onset DM group. Perioperatively, the optimal controlled DM group had the highest TAR (26.7 % [11.3–49.0]) while the new-onset and suboptimal controlled DM group had TARs of 4.6 % [1.2–9.6] and 16.3 % [11.5–23.4], respectively.</div></div><div><h3>Conclusions</h3><div>Blinded CGM revealed frequent pre- and perioperative hyperglycaemia and high inter-individual variability in TAR among patients with (new-onset) DM undergoing pancreatic surgery. These findings support the need for stricter and more individualized glucose monitoring. This could optimize preoperative glucose management and thereby possibly reduce postoperative complications.</div></div>","PeriodicalId":46328,"journal":{"name":"Journal of Clinical and Translational Endocrinology","volume":"43 ","pages":"Article 100426"},"PeriodicalIF":3.3,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145685823","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of cyclic yoga on selected metabolic and hepatic parameters in diabetic women with fatty liver diseases: A clinical trial","authors":"Zahra Bayat ,&nbsp;Seyedeh Soolmaz Mahdioun ,&nbsp;Houshang Nemati ,&nbsp;Fatemeh Rezvan Madani ,&nbsp;Mehrali Rahimi ,&nbsp;Hanieh Dehghan ,&nbsp;Rozita Naseri ,&nbsp;Seyed Mehdi Goosheh","doi":"10.1016/j.jcte.2026.100431","DOIUrl":"10.1016/j.jcte.2026.100431","url":null,"abstract":"<div><h3>Aims</h3><div>Type 2 diabetes mellitus and non-alcoholic fatty liver disease increase cardiometabolic risk. This randomized controlled trial assessed the effects of cyclic yoga, a structured asana sequence, on anthropometric, glycemic, lipid, and hepatic parameters in overweight women with both conditions.</div></div><div><h3>Methods</h3><div>Forty overweight women (mean age 50.5 ± 5.5 years) with type 2 diabetes and non-alcoholic fatty liver disease were randomized to either an eight-week cyclic yoga intervention (three sessions/week) or a control group maintaining usual activities. Pre- and post-intervention, fasting blood glucose, glycated hemoglobin, insulin resistance, lipid profile, liver enzymes (alanine aminotransferase, aspartate aminotransferase), anthropometric parameters were measured and analyzed using repeated measures analysis of variance.</div></div><div><h3>Results</h3><div>The cyclic yoga group showed significant reductions in fasting blood glucose, glycated hemoglobin, insulin resistance, triglycerides, low-density lipoprotein cholesterol, alanine aminotransferase, aspartate aminotransferase, weight, body mass index, hip circumference, waist circumference, with increased high-density lipoprotein cholesterol compared to control group.</div></div><div><h3>Conclusions</h3><div>Cyclic yoga appears to improve glycemic control, lipid profiles, liver enzymes, and anthropometric indices in women with type 2 diabetes mellitus and non-alcoholic fatty liver disease. These findings suggest that cyclic yoga may be a safe, practical, and cost-effective complementary therapy to improve metabolic and hepatic health in this high-risk population, although larger and longer term studies are warranted.</div></div>","PeriodicalId":46328,"journal":{"name":"Journal of Clinical and Translational Endocrinology","volume":"43 ","pages":"Article 100431"},"PeriodicalIF":3.3,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146077938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Non-alcoholic fatty pancreas disease (NAFPD) as a pre-neoplastic niche: Metabolic and inflammatory Gateways to pancreatic ductal adenocarcinoma","authors":"Hope Onohuean ,&nbsp;Ngozi F. Nnolum-Orji ,&nbsp;Sarad Pawar Naik Bukke ,&nbsp;Kasim Sakran Abass ,&nbsp;Abdullateef Isiaka Alagbonsi ,&nbsp;Yahya E. Choonara","doi":"10.1016/j.jcte.2025.100424","DOIUrl":"10.1016/j.jcte.2025.100424","url":null,"abstract":"<div><div>Non-alcoholic fatty pancreas disease (NAFPD), marked by ectopic triglyceride accumulation in the exocrine pancreas, is increasingly observed yet its recognition as a cancer-predisposing condition remains limited. We synthesize evidence supporting NAFPD as an early and modifiable niche for pancreatic ductal adenocarcinoma (PDAC), using a PRISMA-ScR-guided framework. The findings were synthesized into three domains: epidemiological risk, metabolic–inflammatory signaling, and immune–stromal remodeling. Mechanisms include palmitate-induced ER stress, ROS-driven NLRP3–IL-1β and STAT5 signaling, and KRAS^G12D-mediated lipotoxicity. Lipid-laden stellate cells promote fibrosis, immunosuppression, and epithelial–mesenchymal transition. NAFPD may represent an early, modifiable PDAC niche, warranting further imaging–omic studies and targeted prevention trials.</div></div>","PeriodicalId":46328,"journal":{"name":"Journal of Clinical and Translational Endocrinology","volume":"42 ","pages":"Article 100424"},"PeriodicalIF":3.3,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145520206","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alternative approaches to glucose measurements during oral glucose tolerance testing in youth with cystic fibrosis: a mixed methods pilot study","authors":"Seema Meighan ,&nbsp;Robert J. Gallop ,&nbsp;Melissa S. Putman ,&nbsp;Andrea Kelly ,&nbsp;Brynn E. Marks","doi":"10.1016/j.jcte.2025.100421","DOIUrl":"10.1016/j.jcte.2025.100421","url":null,"abstract":"<div><h3>Background</h3><div>Adherence to annual OGTT screening for cystic fibrosis-related diabetes (CFRD) is poor. In this mixed methods study we assessed the accuracy, feasibility, and acceptability of alternative approaches to glucose measurements during an OGTT.</div></div><div><h3>Methods</h3><div>Standard OGTT with plasma glucose sampling at 0, 60, and 120-min was conducted in 14 youth ≥ 10 years of age with CF. A self-administered OGTT kit (Digostics, GTT@home) measuring capillary glucose and Dexcom G7 continuous glucose monitoring (CGM) were performed concomitantly with OGTT. CGM glucose values were recorded at 5-minute intervals for 20-minutes after each time point to account for lag. Plasma OGTT glucose and glucose tolerance categories [normal (NGT), impaired (IGT), indeterminate (INDET), and CFRD] were compared with these same outcomes as defined by the self-administered kit and CGM. Younden’s index was used to determine the optimal CGM timepoint for categorization of glucose tolerance, and ROC curves were used to identify the optimal glucose thresholds. Participants and their parents were interviewed to understand their experience with alternative testing approaches.</div></div><div><h3>Results</h3><div>Based on plasma glucose, participants were characterized as NGT (n = 8), IGT (n = 5), and CFRD (n = 1). Whereas the GTT@home correctly categorized glucose tolerance in 6 participants (43 %), CGM correctly categorized 13 (93 %). The CGM glucose at 125 min was identified as the timepoint at which the measured glucose yielded maximum discrimination for all categories of glucose tolerance (AUC for NGT = 0.979, IGT = 0.867, CFRD = 1.0). A CGM glucose threshold of 154 mg/dL demonstrated 100 % sensitivity and 87.5 % specificity for identifying NGT; for IGT a threshold of 182 mg/dL exhibited 80 % sensitivity and 88.9 % specificity. Parent-child dyads valued convenience during OGTT screening, but expressed concerns about glucose measurement accuracy and performing medical procedures in the home.</div></div><div><h3>Conclusions</h3><div>CGM glucose values during OGTT may offer an accurate assessment of glucose tolerance categories, though this approach may require further refinement for patient acceptability.</div></div>","PeriodicalId":46328,"journal":{"name":"Journal of Clinical and Translational Endocrinology","volume":"42 ","pages":"Article 100421"},"PeriodicalIF":3.3,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145520207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hormone responses to buserelin in polycystic ovary syndrome and in eumenorrheic women with hyperandrogenism/hyperandrogenemia, and the relationship of these responses with insulin resistance","authors":"Salvatore Benvenga ,&nbsp;Michele Russo ,&nbsp;Fausto Famà ,&nbsp;Gianpiero Forte ,&nbsp;Vittorio Unfer","doi":"10.1016/j.jcte.2025.100420","DOIUrl":"10.1016/j.jcte.2025.100420","url":null,"abstract":"<div><div>We compared 37 women with polycystic ovary syndrome (PCOS) with 24 women with eumenorrhea plus hyperandrogenism and/or hyperandrogenemia without ultrasound evidence of PCO morphology (EuHyperA) to assess their hormone responses to a GnRH-agonist (buserelin). Following our recent paper on PCOS and EuHyperA, we selected patients who performed the 2 h-oral glucose tolerance test (OGTT), and stratified them according to presence/absence of insulin resistance (IR), <em>viz.</em> HOMA-index ≥ 2.5.</div><div>IR impacted on the PCOS group since IR-yes-PCOS women had significantly higher body weight, BMI, total testosterone (TT), free androgen index (FAI), and 17-hydroxyprogesterone (17-OHP), borderline higher delta-4 androstenedione (Δ4-ASD) and ovarian volume, and significantly lower sex hormone-binding globulin (SHBG) <em>vs</em> IR-no-PCOS. IR-no-EuHyperA had significantly higher follicle-stimulating hormone (FSH), borderline higher dehydroepiandrosterone sulfate (DHEAS) and borderline lower 17-OHP <em>vs</em> IR-no-PCOS. IR-yes-EuHyperA had significantly higher DHEAS, borderline lower TT and FAI <em>vs</em> IR-yes-PCOS.</div><div>The insulin curve was significantly higher in the IR-yes <em>vs</em> IR-no-PCOS, and IR-yes <em>vs</em> IR-no-EuHyperA. Compared to PCOS, EuHyperA had insignificantly lower glucose and insulin responses regardless of IR status.</div><div>After steroidogenic ovarian stimulation (24 h-buserelin test), IR presence <em>vs</em> IR absence impacted on 4 curves in PCOS (significantly higher TT, borderline higher 17-OHP, significantly lower Δ4-ASD and DHEAS), and only one curve in EuHyperA (significantly higher TT). IR-no-EuHyperA had two curves significantly lower than IR-no-PCOS (Δ4-ASD and TT). Instead, IR-yes-EuHyperA had significantly lower Δ4-ASD, TT and 17-OHP curves, and significantly higher DHEAS curve <em>vs</em> IR-yes-PCOS.</div><div>In conclusion, of 35 parameters (baseline, OGTT-related, buserelin-related), 28 (80%) were statistically similar in EuHyperA <em>vs</em> PCOS regardless of IR status. However, IR presence impacted on more parameters in PCOS than EuHyperA. Given the known ovary sparing by IR in PCOS, it appears that IR exacerbates androgen production of PCOS women more markedly than EuHyperA women.</div></div>","PeriodicalId":46328,"journal":{"name":"Journal of Clinical and Translational Endocrinology","volume":"42 ","pages":"Article 100420"},"PeriodicalIF":3.3,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145227856","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Insights into intramuscular adipose–muscle signaling in the diabetic lower extremity","authors":"Chang Gui ,&nbsp;Dakota R. Kamm ,&nbsp;Jeremie L.A. Ferey ,&nbsp;Kathryn L. Bohnert ,&nbsp;Jeremy J. McCormick ,&nbsp;Mary K. Hastings ,&nbsp;Gretchen A. Meyer","doi":"10.1016/j.jcte.2025.100422","DOIUrl":"10.1016/j.jcte.2025.100422","url":null,"abstract":"<div><div>Intramuscular adipose tissue (IMAT) has been proposed to directly contribute to myofiber dysfunction through paracrine signaling. The impacts of this signaling beyond contributing to myofiber insulin resistance are largely unknown. This study aims to explore the human IMAT transcriptome, with a focus on its potential role in myoblast fusion deficits in advanced muscle pathology. Using a within-subjects design, we compared IMAT to subcutaneous (SQ) fat in individuals with and without diabetes undergoing below-knee amputation. We hypothesized that IMAT from the diabetic group would exhibit a pro-inflammatory profile, similar to diabetic SQ, and that inflammatory secreted factors from IMAT progenitors would impair cultured myoblast fusion. Instead, we found that the IMAT transcriptome from the diabetic group exhibited reduced enrichment of inflammatory pathways compared with SQ and less transcriptional evidence for immune cell infiltration. While IMAT featured a mostly anti-myogenic transcriptional profile for secreted cytokines, media conditioned by IMAT progenitors did not uniquely impair fusion of cultured myoblasts compared with SQ. Surprisingly, the diabetic status of the myoblast donor predicted myoblast fusion, with reduced fusion rates in diabetic myoblasts exposed to conditioned media from all adipose sources. This suggests that IMAT-myoblast signaling may be detrimental to regeneration in diabetes, but that the effect is driven in part by an intrinsic difference in diabetic myoblasts’ sensitivity to IMAT secreted factors. This emphasizes the insight that can be gained from disease-state matched and mismatched culture models and highlights the need to better understand how diabetes impacts myoblasts and their interaction with the disease environment.</div></div>","PeriodicalId":46328,"journal":{"name":"Journal of Clinical and Translational Endocrinology","volume":"42 ","pages":"Article 100422"},"PeriodicalIF":3.3,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145418190","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Insulin dose adjustment policy for certified diabetes care and education specialists: Safe and effective","authors":"Jeannine C. Leverenz ,&nbsp;Lauren Horton ,&nbsp;Barry Conrad ,&nbsp;Shannon Lin ,&nbsp;Annette Chmielewski ,&nbsp;Franziska K. Bishop ,&nbsp;Melissa Quaid ,&nbsp;Priya Prahalad ,&nbsp;David M. Maahs","doi":"10.1016/j.jcte.2025.100423","DOIUrl":"10.1016/j.jcte.2025.100423","url":null,"abstract":"<div><div>In 4T Study 1, youth with new-onset type 1 diabetes started a continuous glucose monitor (CGM) soon after diagnosis and received remote CGM data review and dose changes by a Certified Diabetes Care and Education Specialist (CDCES) via secure portal messaging. We describe the CDCES policy to make incremental dose adjustments and report its safety and effectiveness, which facilitated patients’ reaching and maintaining targets. We aim to publish this data-supported CDCES protocol to facilitate use at other diabetes centers who may restrict CDCES from adjusting insulin doses.</div><div>The CDCESs and Pediatric Endocrinologists agreed on criteria for making dose changes. CDCESs made insulin dose adjustments and consulted with Pediatric Endocrinologists per protocol and as needed. CDCES sent messages with suggested dose adjustments and behavior changes via secure portal messaging.</div><div>In the first year, a total of 1564 remote patient monitoring messages were sent to 133 participants. Most messages were triggered by low time-in-range (TIR, 70–180 mg/dl [63 %]), hypoglycemia (39 %), decline in TIR (13 %), or insufficient CGM wear time (7 %). There were 3 episodes of severe hypoglycemia, none adjudicated related to the CDCES dosing protocol. At one year, the mean time &lt;70 mg/dl was &lt;2 %, and the A1C target of &lt;7 % was met by 64 %.</div><div>We created a policy for CDCESs to adjust insulin doses and increase patient interaction between visits. The results demonstrate that CDCES can work at the top of their certification to adjust insulin doses to achieve target goals without decreasing safety.</div></div>","PeriodicalId":46328,"journal":{"name":"Journal of Clinical and Translational Endocrinology","volume":"42 ","pages":"Article 100423"},"PeriodicalIF":3.3,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145467357","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DiaBar: Predicting type 2 diabetes remission post-metabolic surgery utilizing mRNA expression profiles from subcutaneous adipose tissue","authors":"Jonas Wagner ,&nbsp;Manfred Wischnewsky ,&nbsp;Patricia von Kroge ,&nbsp;Helge Wilhelm Thies ,&nbsp;Pia Roser ,&nbsp;Stefan Wolter ,&nbsp;Thilo Hackert ,&nbsp;Jakob Izbicki ,&nbsp;Oliver Mann ,&nbsp;Anna Duprée","doi":"10.1016/j.jcte.2025.100410","DOIUrl":"10.1016/j.jcte.2025.100410","url":null,"abstract":"<div><h3>Background</h3><div>Subcutaneous adipose tissue (SAT) is a metabolic organ, which is involved in the pathogenesis of type 2 diabetes (T2D). Methods to predict diabetes remission after metabolic surgery exist, however their prediction accuracy still needs improvement. We hypothesized, that gene expression profiles in the SAT could predict diabetes remission after metabolic surgery more accurately than any current methods.</div></div><div><h3>Methods</h3><div>In this retrospective cohort study, we identified individuals who underwent metabolic surgery. We collected SAT biopsies during the surgery and analyzed the expression of <em>HMGA2</em>, <em>PPARG</em>, <em>ADIPOQ</em> and, <em>IL6</em>. The American Diabetes Association criteria were used to define partial and complete remission. Univariate generalized linear models, tree decision algorithms (Exhausted Chaid, CART and Quinlan’s C5 with adaptive boosting) and, multilayer perceptron networks were used to develop classifiers for patients with no, partial or complete remission (DiaBar).</div></div><div><h3>Results</h3><div>In this study 106 patients were included, 66 (62.3%) patients had T2D the remaining 40 (37.7%) were patients with prediabetes. Complete and partial remission were achieved by 69 (65.1%) and 20 (18.9%) patients respectively. Using a multilayer perceptron, we achieved an overall accuracy of 98.0% (remission: no 100%; partial 90.0%; complete 100%). The validated DiaRem Score was used as the comparative score, which had an overall accuracy for classifying patients with complete, partial or no remission of 74.7%.</div></div><div><h3>Conclusions</h3><div>Using gene expression profiles from the SAT, we developed the DiaBar test, which accurately predicts diabetes remission after metabolic surgery and seems to be superior to the DiaRem score.</div></div>","PeriodicalId":46328,"journal":{"name":"Journal of Clinical and Translational Endocrinology","volume":"41 ","pages":"Article 100410"},"PeriodicalIF":4.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144694403","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Decreased insulin dose-adjusted hemoglobin A1c in adults with cystic fibrosis-related diabetes treated with elexacaftor-tezacaftor-ivacaftor","authors":"Espérie Burnet ,&nbsp;Deborah Grunewald ,&nbsp;Etienne Larger ,&nbsp;Florence Camus-Bablon ,&nbsp;Catherine Eisenhauer ,&nbsp;François Mifsud ,&nbsp;Clémence Martin ,&nbsp;Isabelle Honoré ,&nbsp;Reem Kanaan ,&nbsp;Nicolas Carlier ,&nbsp;Johanna Fesenbeckh ,&nbsp;Helen Mosnier-Pudar ,&nbsp;Pierre-Régis Burgel","doi":"10.1016/j.jcte.2025.100407","DOIUrl":"10.1016/j.jcte.2025.100407","url":null,"abstract":"<div><h3>Background</h3><div>Elexacaftor-tezacaftor-ivacaftor (ETI) became available for adults with cystic fibrosis (CF) in 2019, but its impact on CF-related diabetes (CFRD) remains unclear.</div></div><div><h3>Methods</h3><div>A single-center retrospective cohort study was conducted among adults with CFRD to examine the change in insulin dose-adjusted Hemoglobin A1c (IDAA1c). Linear mixed effects model (LMEM) analysis was used to investigate the change in IDAA1c between baseline and 24 months of follow up, comparing an ETI-treated group to an unexposed group. Baseline values were those documented at treatment initiation for the ETI-treated group and in March 2020 (±3 months) for the unexposed group.</div></div><div><h3>Results</h3><div>A total of 49 adults were included, 39 were treated with ETI and 10 were not. Median [Interquartile range] time since CFRD diagnosis at baseline was 13 [7–18] and 14 [10–18] years, respectively (p = 0.610). In the ETI-treated group, mean weight increased by a 4.44 kg (95 % Confidence Interval, 95 %CI: 3.08 to 5.79, p &lt; 0.001), insulin total daily dose decreased by 5 units (95 %CI: −9 to 0, p = 0.033), and hemoglobin A1c (%) decreased by 0.65 points (95 %CI: −0.96 to −0.34, p &lt; 0.001). No change was observed in the unexposed group. LMEM analysis found a numerically significant association between ETI and decreased IDAA1c, estimated at −1.14 points (95 %CI: −2.35 to 0.06, p = 0.067) after adjusting for age, sex, time since CFRD diagnosis and the introduction of Metformin.</div></div><div><h3>Conclusion</h3><div>A numerically significant association between ETI and IDAA1c decrease was observed in adults with established CFRD after 24 months of treatment, suggesting ETI contributed to improved glycemic control.</div></div>","PeriodicalId":46328,"journal":{"name":"Journal of Clinical and Translational Endocrinology","volume":"41 ","pages":"Article 100407"},"PeriodicalIF":4.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144571328","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}