Journal of Clinical Endocrinology & Metabolism最新文献

{"title":"Associations of Regional Body Fat With Risk of Cardiovascular Disease and Mortality Among Individuals With Type 2 Diabetes.","authors":"Zixin Qiu, Dong Hoon Lee, Qi Lu, Rui Li, Kai Zhu, Lin Li, Ruyi Li, An Pan, Edward L Giovannucci, Gang Liu","doi":"10.1210/clinem/dgae192","DOIUrl":"10.1210/clinem/dgae192","url":null,"abstract":"<p><strong>Context: </strong>It is largely unknown whether regional fat accumulation is associated with risk of cardiovascular disease (CVD) and mortality among individuals with type 2 diabetes (T2D), who often exhibit changes in relative fat distribution and have increased CVD risk.</p><p><strong>Objective: </strong>To prospectively examine the association between regional body fat and risk of CVD in individuals with T2D and to determine whether the associations are independentof traditional measures of obesity.</p><p><strong>Methods: </strong>The main analysis included 21 472 participants with T2D from the UK Biobank. Regional body fat was measured by bioelectric impedance assessment. Cox proportional-hazards regression models were used to estimate hazard ratios (HRs) and 95% CIs.</p><p><strong>Results: </strong>Over a median of 7.7 years of follow-up, 3976 CVD events occurred. After multivariable adjustment, upper and lower body fat were independently and oppositely associated with CVD risk among patients with T2D. Higher arm fat percentage was linearly associated with increased CVD risk (Pnonlinear > .05), while higher trunk fat percentage was nonlinearly associated with increased CVD risk (Pnonlinear < .05). In contrast, higher leg fat percentage was nonlinearly associated with lower CVD risk (Pnonlinear < .05). When comparing extreme quartiles, the multivariable-adjusted HR (95% CI) of CVD was 0.72 (0.58-0.90) for leg fat percentage, 1.63 (1.29-2.05) for arm fat percentage, and 1.27 (1.06-1.52) for trunk fat percentage. Similar patterns of associations were observed for all-cause and CVD mortality. In addition, leg fat percentage, but not other regional fat percentage, was associated with CVD risk independently of traditional measures of obesity.</p><p><strong>Conclusion: </strong>Among people with T2D, arm fat and trunk fat were positively, whereas leg fat was inversely, associated with the risk of CVD and mortality. These findings highlight the importance of considering both the amount and the location of body fat when assessing CVD and mortality risk among individuals with T2D.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":"e372-e381"},"PeriodicalIF":5.0,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140289482","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel Biomarkers Reveal Mismatch Between Tissue and Serum Thyroid Hormone Status in Amiodarone-Induced Hyperthyroidism.","authors":"Richárd Sinkó, Mónika Katkó, Géza Tóth, Gábor László Kovács, Orsolya Dohán, Tibor Fülöp, Patrício Costa, Beáta Dorogházi, Dóra Kővári, Endre V Nagy, Csaba Fekete, Balázs Gereben","doi":"10.1210/clinem/dgae514","DOIUrl":"10.1210/clinem/dgae514","url":null,"abstract":"<p><strong>Context: </strong>Serum thyrotropin and thyroid hormone (TH) levels are routine markers of thyroid function. However, their diagnostic performance is limited under special conditions, such as in amiodarone-induced hyperthyroidism (AIH). Such cases would require the assessment of tissue TH action, which is currently unfeasible.</p><p><strong>Objective: </strong>Development of an approach that determines how well serum parameters are reflected in tissue TH action of patients.</p><p><strong>Methods: </strong>TH-responsive marker genes were identified from human hair follicles (HFs) with next-generation sequencing, validated by quantitative polymerase chain reaction. A classification model was built with these markers to assess tissue TH action and was deployed on amiodarone-treated patients. The impact of amiodarone on tissue TH action was also studied in thyroid hormone action indicator (THAI) mice.</p><p><strong>Results: </strong>The classification model was validated and shown to predict tissue TH status of subjects with good performance. Serum- and HF-based TH statuses were concordant in hypothyroid and euthyroid amiodarone-treated patients. In contrast, amiodarone decreased the coincidence of serum-based and HF-based TH statuses in patients with hyperthyroidism, indicating that AIH is not unequivocally associated with tissue hyperthyroidism. This was confirmed in the THAI model, where amiodarone prevented tissue hyperthyroidism in THAI mice despite high serum free thyroxine.</p><p><strong>Conclusion: </strong>We developed a minimally invasive approach using HF markers to assess tissue TH economy that could complement routine diagnostics in controversial cases. We observed that a substantial proportion of patients with AIH do not develop tissue hyperthyroidism, indicating that amiodarone protects tissues from thyrotoxicosis. Assessing tissue TH action in patients with AIH may be warranted for treatment decisions.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":"374-386"},"PeriodicalIF":5.0,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11747679/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141793963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Improving the Risk Prediction of the 2015 ATA Recurrence Risk Stratification in Papillary Thyroid Cancer.","authors":"Hongxi Wang, Qianrui Li, Tian Tian, Bin Liu, Rong Tian","doi":"10.1210/clinem/dgae465","DOIUrl":"10.1210/clinem/dgae465","url":null,"abstract":"<p><strong>Background: </strong>Various prognostic factors are expected to refine the American Thyroid Association recurrence risk stratification for patients with papillary thyroid cancer (PTC). However, it remains unclear to what extent integrating these factors improves patient treatment decision-making.</p><p><strong>Methods: </strong>We developed 2 predictive models for structural incomplete response (SIR) at the 1-year follow-up visit, based on comprehensive clinical data from a retrospective cohort of 2539 patients. Model 1 included the recurrence risk stratification and lymph node features (ie, number and ratio of metastatic lymph nodes, N stage). Model 2 further incorporated preablation stimulated thyroglobulin (s-Tg). An independent cohort of 746 patients was used for validation analysis. We assessed the models' predictive performance compared to the recurrence risk stratification using the integrated discrimination improvement (IDI) and the continuous net reclassification improvement (NRI). The clinical utility of the models was evaluated using decision curve analysis.</p><p><strong>Results: </strong>Both model 1 and model 2 outperformed the recurrence risk stratification in predicting SIR, with improved correct classification rates (model 1: IDI = 0.02, event NRI = 42.31%; model 2: IDI = 0.07, event NRI = 53.54%). The decision curves indicated that both models provided greater benefits over the risk stratification system in clinical decision-making. In the validation set, model 2 maintained similar performance while model 1 did not significantly improve correct reclassification.</p><p><strong>Conclusion: </strong>The inclusion of lymph node features and s-Tg showed potential to enhance the predictive accuracy and clinical utility of the existing risk stratification system for PTC patients.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":"534-541"},"PeriodicalIF":5.0,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141565017","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of Initial and Changes in Serum A-FABP Level With the Development and Improvement of Presarcopenia.","authors":"Tingting Hu, Yiting Xu, Xiaoya Li, Yunfeng Xiao, Yufei Wang, Yuqian Bao, Xiaojing Ma","doi":"10.1210/clinem/dgae531","DOIUrl":"10.1210/clinem/dgae531","url":null,"abstract":"<p><strong>Context: </strong>Several cross-sectional studies have reported the association between serum adipocyte fatty acid-binding protein (A-FABP) level and presarcopenia. However, data on the effects of serum A-FABP level and its changes over time on the development and improvement of presarcopenia are scarce.</p><p><strong>Objective: </strong>This study aimed to explore the association of serum A-FABP level with the incidence and improvement of presarcopenia in a community-based cohort, and further investigated the association of changes in serum A-FABP level with the incidence and improvement of presarcopenia.</p><p><strong>Methods: </strong>This longitudinal cohort study included 1496 adults (41.2% men; median age, 58 [53-63] years) in 2013 to 2014 and was followed up to 2015 to 2016. Participants underwent serum A-FABP level measurements at baseline and a follow-up visit. Visceral fat area (VFA) was measured using magnetic resonance imaging. Skeletal muscle mass (SMM) was estimated by bioelectrical impedance analysis and converted to a skeletal muscle index (SMI). Presarcopenia was defined as SMI less than 1 SD of the sex-specific mean for the young reference group.</p><p><strong>Results: </strong>During an average follow-up period of 2.1 years, baseline serum A-FABP level was positively associated with the incidence of presarcopenia (standardized by weight: risk ratio [RR] 3.22; 95% CI, 1.96-5.38; standardized by VFA: RR 2.11, 95% CI, 1.29-3.51) and negatively associated with the improvement of presarcopenia (standardized by weight: RR 0.66; 95% CI, 0.45-0.97; standardized by VFA: RR 0.71; 95% CI, 0.54-0.94), regardless of whether SMM was standardized by weight or VFA. Moreover, changes in serum A-FABP level provided additional information on the incidence and improvement of presarcopenia, independent of baseline serum A-FABP level (all P < .05).</p><p><strong>Conclusion: </strong>Baseline serum A-FABP level and its changes were positively associated with the incidence and negatively associated with the improvement of presarcopenia.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":"345-355"},"PeriodicalIF":5.0,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141890699","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Letter to the Editor From Fu et al: \"Machine Learning Reveals the Contribution of Lipoproteins to Liver Triglyceride Content and Inflammation\".","authors":"Wei Fu, Junlong Zhao, Guobin Chen, Linya Lv","doi":"10.1210/clinem/dgae579","DOIUrl":"10.1210/clinem/dgae579","url":null,"abstract":"","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":"e548-e549"},"PeriodicalIF":5.0,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142005712","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Urine Tricarboxylic Acid Cycle Metabolites and Risk of End-stage Kidney Disease in Patients With Type 2 Diabetes.","authors":"Jian-Jun Liu, Sylvia Liu, Huili Zheng, Janus Lee, Resham L Gurung, Clara Chan, Lye Siang Lee, Keven Ang, Jianhong Ching, Jean-Paul Kovalik, Subramaniam Tavintharan, Chee Fang Sum, Kumar Sharma, Thomas M Coffman, Su Chi Lim","doi":"10.1210/clinem/dgae199","DOIUrl":"10.1210/clinem/dgae199","url":null,"abstract":"<p><strong>Context: </strong>Metabolites in the tricarboxylic acid (TCA) pathway have pleiotropic functions.</p><p><strong>Objective: </strong>To study the association between urine TCA cycle metabolites and the risk for chronic kidney disease progression in individuals with type 2 diabetes.</p><p><strong>Design, setting and participants: </strong>A prospective study in a discovery (n = 1826) and a validation (n = 1235) cohort of people with type 2 diabetes in a regional hospital and a primary care facility.</p><p><strong>Exposure and outcome: </strong>Urine lactate, pyruvate, citrate, alpha-ketoglutarate, succinate, fumarate, and malate were measured by mass spectrometry. Chronic kidney disease progression was defined as a composite of sustained estimated glomerular filtration rate below 15 mL/min/1.73 m2, dialysis, renal death, or doubling of serum creatinine.</p><p><strong>Results: </strong>During a median of 9.2 (interquartile range 8.1-9.7) and 4.0 (3.2-5.1) years of follow-up, 213 and 107 renal events were identified. Cox regression suggested that urine lactate, fumarate, and malate were associated with an increased risk (adjusted hazard ratio, [95% CI] 1.63 [1.16-2.28], 1.82 [1.17-2.82], and 1.49 [1.05-2.11], per SD), whereas citrate was associated with a low risk (aHR 0.83 [0.72-0.96] per SD) for the renal outcome after adjustment for cardiorenal risk factors. These findings were reproducible in the validation cohort. Noteworthy, fumarate and citrate were independently associated with the renal outcome after additional adjustment for other metabolites.</p><p><strong>Conclusion: </strong>Urine fumarate and citrate predict the risk for progression to end-stage kidney disease independent of clinical risk factors and other urine metabolites. These 2 metabolites in TCA cycle pathway may play important roles in the pathophysiological network, underpinning progressive loss of kidney function in patients with type 2 diabetes.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":"e321-e329"},"PeriodicalIF":5.0,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140307681","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Growth Trajectories of Children Born Preterm and Full-Term With Low Birth Weight to Preschool Ages: A Nationwide Study.","authors":"Jong Ho Cha, Eungu Kang, Jae Yoon Na, Soorack Ryu, Young-Jin Choi, Ja Hye Kim","doi":"10.1210/clinem/dgae208","DOIUrl":"10.1210/clinem/dgae208","url":null,"abstract":"<p><strong>Context: </strong>Preterm (PT) and full-term with low birth weight (FT-LBW) children are at a high-risk of poor growth outcomes.</p><p><strong>Objective: </strong>This work aimed to investigate the growth trajectories of PT and FT-LBW children from birth to preschool ages.</p><p><strong>Methods: </strong>This study included 1 150 508 infants (PT, 41 454; FT-LBW, 38 250) who underwent the first 3 rounds (4-6, 9-12, and 18-24 months) of the National Health Screening Program for Infants and Children (NHSPIC). Growth measurements were obtained from the NHSPIC database and converted into Z-scores. Growth data at ages 2, 4, and 6 years were measured as outcome variables. The effect of being born small on poor growth outcomes was investigated using a generalized estimating equation and Cox proportional-hazards regression analysis.</p><p><strong>Results: </strong>The median birth weights of the PT, FT-LBW, and FT groups were 2.3, 2.4, and 3.2 kg, respectively. The incidence of short stature (height Z-score < -2 SD score [SDS]) and failure to thrive (FTT) (body mass index (BMI) Z-score < -2 SDS) was the highest in the FT-LBW group, followed by the PT and FT groups. At age 4 years, the incidence rates were 6.0% vs 5.2% vs 1.9% for short stature and 4.6% vs 3.9% vs 1.7% for FTT. The β estimate of height outcome was lower both in the PT (-0.326 SDS) and FT-LBW (-0.456 SDS) groups.</p><p><strong>Conclusion: </strong>The FT-LBW group was consistently shorter and lighter throughout the preschool period than the PT group, highlighting the significance of growth monitoring in high-risk populations.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":"e283-e293"},"PeriodicalIF":5.0,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140337468","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LDL-C and TC Mediate the Risk of PNPLA3 Inhibition in Cardiovascular Diseases.","authors":"Genshan Zhang, Wei Jiang, Fangxun He, Jie Fu, Xiangshang Xu, Xuelai Luo, Zhixin Cao","doi":"10.1210/clinem/dgae264","DOIUrl":"10.1210/clinem/dgae264","url":null,"abstract":"<p><strong>Context: </strong>PNPLA3 is a promising target for the treatment of metabolic dysfunction-associated steatotic liver disease. ARO-PNPLA3 is a drug that efficiently lowers PNPLA3 expression in hepatocytes at the mRNA level, resulting in a significant reduction in liver fat in Phase I clinical trials. However, the long-term effects and potential side effects of ARO-PNPLA3 are not well understood.</p><p><strong>Objective: </strong>We conducted a 2-sample, 2-step Mendelian randomization analysis to investigate the association between PNPLA3 inhibition and 10 cardiovascular diseases (CVDs), as well as the role of lipid traits as mediators.</p><p><strong>Methods: </strong>We identified genetic variants near the PNPLA3 gene, which are linked to liver fat percentage, as instrumental variables for inhibiting PNPLA3. Additionally, positive control analyses on liver diseases were conducted to validate the selection of the genetic instruments.</p><p><strong>Results: </strong>Genetically predicted PNPLA3 inhibition significantly increased the risk of coronary atherosclerosis (1.14, 95% CI 1.06, 1.23), coronary heart disease (1.14, 95% CI 1.08, 1.21), and myocardial infarction (1.16, 95% CI 1.08, 1.26). Suggestive associations were observed for increased risk of heart failure (1.09, 95% CI 1.02, 1.17, P = .0143) and atrial fibrillation (1.17, 95% CI 1.00, 1.36, P = .0468). Blood low-density lipoprotein cholesterol (LDL-C) and total cholesterol (TC) mediated approximately 16% to 25%, 16% to 30%, and 14% to 22% of the associations between PNPLA3 inhibition and coronary atherosclerosis, myocardial infarction, and coronary heart disease, respectively.</p><p><strong>Conclusion: </strong>This study suggests that PNPLA3 inhibition increases the risk of major CVDs. Moreover, blood LDL-C and TC may mediate a significant proportion of the associations between PNPLA3 inhibition and coronary atherosclerosis, coronary heart disease, or myocardial infarction.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":"e231-e238"},"PeriodicalIF":5.0,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140870294","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of Physical Activity Patterns With Nocturnal Hypoglycemia Events in Youth With Type 1 Diabetes.","authors":"Ignacio Hormazábal-Aguayo, Nidia Huerta-Uribe, Jacinto Muñoz-Pardeza, Yasmin Ezzatvar, Mikel Izquierdo, Antonio García-Hermoso","doi":"10.1210/clinem/dgae451","DOIUrl":"10.1210/clinem/dgae451","url":null,"abstract":"<p><strong>Aims: </strong>This study sought to elucidate the interactions among physical activity (PA) patterns, mean glucose concentrations, and the incidence of nocturnal hypoglycemia events in children and adolescents with type 1 diabetes, examining the moderating influence of daily dosage on these associations.</p><p><strong>Methods: </strong>Eighty-two participants aged 6 to 18 years (43.9% girls) from the Diactive-1 Cohort Study, diagnosed with type 1 diabetes, were included. Data collection involved continuous glucose monitoring, accelerometry to assess real-world PA, as well as documentation of daily insulin doses and carbohydrate counting over the same 7 days.</p><p><strong>Results: </strong>A total of 19 participants experienced at least 1 nocturnal hypoglycemia event over a span of 574 measurement days (106 days with and 451 days without nocturnal hypoglycemia). Higher levels of vigorous PA (VPA) were associated with lower same-day mean glucose levels (P = .014). Additionally, higher levels of moderate PA (P = .023), VPA (P = .011), and moderate-to-vigorous PA (P = .010) were associated with a greater number of nocturnal hypoglycemia events. Specifically, a significant association was identified between VPA and nocturnal hypoglycemia events when the daily insulin dose was at or above 1.04 units per kilogram of body weight per day (P = .016).</p><p><strong>Conclusion: </strong>Daily VPA is associated with glucose reductions, potentially leading to more hypoglycemic episodes, particularly when there is an excess of daily insulin. This highlights the need for careful insulin management in children and adolescents with type 1 diabetes engaging in VPA.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":"564-571"},"PeriodicalIF":5.0,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11747692/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141494097","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical and Genetic Characteristics of Congenital Hyperinsulinism in Norway: A Nationwide Cohort Study.","authors":"Christoffer Drabløs Velde, Janne Molnes, Siren Berland, Pål Rasmus Njølstad, Anders Molven","doi":"10.1210/clinem/dgae459","DOIUrl":"10.1210/clinem/dgae459","url":null,"abstract":"<p><strong>Purpose: </strong>Congenital hyperinsulinism (CHI) is a rare, monogenic disease characterized by excessive insulin secretion. We aimed to evaluate all probands with suspected CHI in Norway registered over the past 2 decades.</p><p><strong>Methods: </strong>The study included 98 probands. Clinical data were cumulated from medical records. All probands were screened for variants in the genes ABCC8 and KCNJ11. Other CHI-related genes were Sanger-sequenced as indicated by the patients' phenotype (n = 75) or analyzed by next-generation sequencing employing a panel of 30 CHI-related genes (n = 23).</p><p><strong>Results: </strong>Twenty-one probands (21%) received a diagnosis other than CHI, the most common being idiopathic ketotic hypoglycemia (9%) or syndromic hyperinsulinism (4%). In the final cohort of 77 CHI probands, genetic findings were revealed in 46 (60%). ABCC8 variants were most common (n= 40), and 5 novel variants were identified. One proband harbored both the pathogenic GCK variant p.(Ala456Val) and the ABCC8 variant p.(Gly505Cys). Although most ABCC8 variants caused immediate disease onset with severe hypoglycemia and were diazoxide-unresponsive, 8 probands had a heterozygous, apparently dominant variant with milder phenotype. Two probands had pathogenic variants in GLUD1, whereas variants in HADH, HNF4A, KCNJ11, and HK1 were identified in 1 proband each, the latter being noncoding. Neurologic sequelae were reported in 53% of the CHI probands. Of nonsurgically treated probands, 43% had spontaneous resolution. The minimum birth prevalence of CHI in Norway is 1:19,400 live births.</p><p><strong>Main conclusion: </strong>Individuals with disease-causing ABCC8 variants dominated our cohort. Patients with known genetic etiology had earlier and more severe disease onset than genetically unsolved patients.</p>","PeriodicalId":50238,"journal":{"name":"Journal of Clinical Endocrinology & Metabolism","volume":" ","pages":"554-563"},"PeriodicalIF":5.0,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11747666/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141535831","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}