المؤلفون: Trico, Domenico, McCollum, Sarah, Samuels, Stephanie, Santoro, Nicola, Galderisi, Alfonso, Groop, Leif, Caprio, Sonia, Shabanova, Veronika

المصدر: Diabetes Care EXODIAB: Excellence of Diabetes Research in Sweden. 45(8):1841-1851

مصطلحات موضوعية: Medicin och hälsovetenskap, Klinisk medicin, Endokrinologi och diabetes, Medical and Health Sciences, Clinical Medicine, Endocrinology and Diabetes

الوصف: In a large, multiethnic cohort of youths with obesity, we analyzed pathophysiological and genetic mechanisms underlying variations in plasma glucose responses to a 180 min oral glucose tolerance test (OGTT). RESEARCH DESIGN AND METHODS Latent class trajectory analysis was used to identify various glucose response profiles to a nine-point OGTT in 2,378 participants in the Yale Pathogenesis of Youth-Onset T2D study, of whom 1,190 had available TCF7L2 genotyping and 358 had multiple OGTTs over a 5 year follow-up. Insulin sensitivity, clearance, and b-cell function were estimated by glucose, insulin, and C-peptide modeling. RESULTS Four latent classes (1 to 4) were identified based on increasing areas under the curve for glucose. Participants in class 3 and 4 had the worst metabolic and genetic risk profiles, featuring impaired insulin sensitivity, clearance, and b-cell function. Model-predicted probability to be classified as class 1 and 4 increased across ages, while insulin sensitivity and clearance showed transient reductions and b-cell function progressively declined. Insulin sensitivity was the strongest determinant of class assignment at enrollment and of the longitudinal change from class 1 and 2 to higher classes. Transitions between classes 3 and 4 were explained only by changes in b-cell glucose sensitivity. CONCLUSIONS We identified four glucose response classes in youths with obesity with different genetic risk profiles and progressive impairment in insulin kinetics and action. Insulin sensitivity was the main determinant in the transition between lower and higher glucose classes across ages. In contrast, transitions between the two worst glucose classes were driven only by b-cell glucose sensitivity.

الوصول الحر: https://lup.lub.lu.se/record/be9039aa-5b1a-4c5f-bc56-d3b19b4ee36dTest
http://dx.doi.org/10.2337/dc22-0110Test

المؤلفون: Viola, Nicola, Agate, Laura, Caprio, Sonia, Lorusso, Loredana, Brancatella, Alessandro, Ricci, Debora, Sgrò, Daniele, Ugolini, Clara, Piaggi, Paolo, Vitti, Paolo, Elisei, Rossella, Santini, Ferruccio, Latrofa, Francesco

المساهمون: Viola, Nicola, Agate, Laura, Caprio, Sonia, Lorusso, Loredana, Brancatella, Alessandro, Ricci, Debora, Sgrò, Daniele, Ugolini, Clara, Piaggi, Paolo, Vitti, Paolo, Elisei, Rossella, Santini, Ferruccio, Latrofa, Francesco

الوصف: Relevance of thyroid autoimmunity to prognosis of papillary thyroid carcinoma is still unsettled. We decided to investigate the impact of thyroid autoimmunity on prognosis of papillary thyroid carcinoma and the handling of TgAbs. We evaluated the clinical course of a large group of patients according to the presence (PTC-LT) or absence (PTC) of lymphocytic thyroiditis at histology. We studied 194 consecutive patients with a diagnosis of PTC and treated with total thyroidectomy plus 131I ablation between 2007 and 2009. Median follow-up (with 25th-75th percentiles) was 84·0 (56·4-118·0) months. The remission criteria were: basal Tg <0·2 ng/mL (or stimulated Tg <1), TgAbs <8 IU/mL (otherwise "decreasing TgAb trend", a decline of ≥20% in sequential TgAb measurements) and unremarkable imaging. PTC-LT and PTC patients had comparable treatment.TgAbs were detectable in 72·5% of PTC-LT and 16·5% of PTC patients. Time to remission was longer in the detectable than in the undetectable TgAb cohort (28·5 vs· 7·5 months [median]; HR 0·54, CI 0·35-0·83, p=0·005). When comparing PTC-LT to PTC patients the difference was maintained in the detectable TgAb (29·3 vs 13·0 months; HR 0·38, CI 0·18-0·80; p=0·01), but not in the undetectable TgAb cohort (7·7 vs 7·3 months; HR 0·90, CI 0·55-1·47; p=0·68). Using the decreasing TgAb trend, the influence of detectable TgAbs on time to remission was abolished. Thyroid autoimmunity does not influence the prognosis of papillary thyroid carcinoma. A decreasing TgAb trend seems an appropriate criterion to establish the remission of papillary thyroid carcinoma.

وصف الملف: ELETTRONICO

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/37043372; info:eu-repo/semantics/altIdentifier/wos/WOS:001042060200007; volume:30; issue:7; firstpage:1; lastpage:9; numberofpages:9; journal:ENDOCRINE-RELATED CANCER; https://hdl.handle.net/11568/1172685Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85160968154; https://erc.bioscientifica.com/view/journals/erc/aop/erc-23-0042/erc-23-0042.xmlTest

الإتاحة: https://doi.org/10.1530/ERC-23-0042Test
https://hdl.handle.net/11568/1172685Test
https://erc.bioscientifica.com/view/journals/erc/aop/erc-23-0042/erc-23-0042.xmlTest

المؤلفون: Tricò, Domenico, Di Sessa, Anna, Caprio, Sonia, Chalasani, Naga, Liu, Wanqing, Liang, Tiebing, Graf, Joerg, Herzog, Raimund I, Johnson, Casey D, Umano, Giuseppina Rosaria, Feldstein, Ariel E, Santoro, Nicola

المصدر: Antioxidants and Redox Signaling. 30(2)

مصطلحات موضوعية: Obesity, Genetics, Nutrition, Prevention, Pediatric, Adolescent, Age Factors, Biomarkers, Child, Delta-5 Fatty Acid Desaturase, Disease Susceptibility, Fatty Acid Desaturases, Female, Gastrointestinal Microbiome, Genetic Background, Genetic Predisposition to Disease, Haplotypes, Humans, Linoleic Acid, Lipid Metabolism, Lipoproteins, Male, Metabolic Syndrome, Metabolome, Oxidation-Reduction, genetic predisposition, gut microbiota, linoleic acid, metabolic syndrome, oxidized low-density lipoproteins, oxidized metabolites of linoleic acid, pediatric obesity, Biochemistry and Cell Biology, Medical Biochemistry and Metabolomics, Pharmacology and Pharmaceutical Sciences, Biochemistry & Molecular Biology

الوصف: We tested whether oxidized linoleic acid metabolites (OXLAM) are associated with pediatric metabolic syndrome (MetS) and a proatherogenic lipoprotein profile in 122 obese adolescents. Furthermore, we examined whether genetic and metagenomic factors can modulate plasma OXLAM concentrations by genotyping the fatty acid desaturase 1/2 (FADS) gene and by characterizing the gut microbiota. Subjects with MetS (n = 50) showed higher concentrations of 9- and 13-oxo-octadecadienoic acid (9- and 13-oxo-ODE) than subjects without MetS (n = 72). Both metabolites were associated with an adverse lipoprotein profile that was characterized by elevated very small-dense low-density lipoprotein (p

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/5bs1q74kTest

المؤلفون: Chiriacò, Martina, Nesti, Lorenzo, Natali, Andrea, Santoro, Nicola, Caprio, Sonia, Tricò, Domenico

المساهمون: European Foundation for the Study of Diabetes, National Institutes of Health

المصدر: Obesity ; volume 31, issue 7, page 1894-1902 ; ISSN 1930-7381 1930-739X

الوصف: Objective A high triglyceride (TG) to high‐density lipoprotein cholesterol (HDL) ratio (TG/HDL) predicts atherosclerosis and cardiovascular events. This study examined whether a proatherogenic distribution of plasma lipoprotein subclasses is associated with a high TG/HDL ratio in youths with obesity. Methods Lipoprotein particle concentration and size were measured by proton nuclear magnetic resonance in a multiethnic cohort of 592 adolescents with overweight/obesity (age 13 ± 3 years, 58% females, BMI z score 2.1 ± 0.8) who were phenotyped with a 3‐hour oral glucose tolerance test and abdominal magnetic resonance imaging. Results The highest TG/HDL quartile showed a higher particle concentration of very low‐density lipoprotein (VLDL; +178%, p < 0.0001), intermediate‐density lipoprotein (+338%, p < 0.0001), and low‐density lipoprotein (LDL; +42%, p < 0.0001), compared with the lowest quartile. The prevalence of large VLDL, very small LDL, and small HDL progressively increased across TG/HDL quartiles. The TG/HDL ratio correlated positively with the average particle size of VLDL ( r = 0.37, p < 0.0001) and negatively with particle size of both LDL ( r = −0.51, p < 0.0001) and HDL ( r = −0.69, p < 0.0001). These associations were independent of sex, age, race/ethnicity, body mass, fasting plasma glucose, and insulin sensitivity. Conclusions In youths with obesity, an elevated TG/HDL ratio is associated with high concentrations of proatherogenic lipoprotein subclasses. This phenotype may explain the increased cardiovascular risk associated with a high TG/HDL ratio.

الإتاحة: https://doi.org/10.1002/oby.23767Test

المؤلفون: Bloyd, Michelle, Sinaii, Ninet, Faucz, Fabio Rueda, Iben, James, Coon, Steven L., Caprio, Sonia, Santoro, Nicola, Stratakis, Constantine A., London, Edra

المساهمون: National Institute of Child Health and Human Development

المصدر: Frontiers in Endocrinology ; volume 14 ; ISSN 1664-2392

مصطلحات موضوعية: Endocrinology, Diabetes and Metabolism

الوصف: Introduction Pediatric obesity has steadily increased in recent decades. Large-scale genome-wide association studies (GWAS) conducted primarily in Eurocentric adult populations have identified approximately 100 loci that predispose to obesity and type II diabetes. GWAS in children and individuals of non-European descent, both disproportionately affected by obesity, are fewer. Rare syndromic and monogenic obesities account for only a small portion of childhood obesity, so understanding the role of other genetic variants and their combinations in heritable obesities is key to developing targeted and personalized therapies. Tight and responsive regulation of the cAMP-dependent protein kinase (PKA) signaling pathway is crucial to maintaining healthy energy metabolism, and mutations in PKA-linked genes represent the most common cause of monogenic obesity. Methods For this study, we performed targeted exome sequencing of 53 PKA signaling-related genes to identify variants in genomic DNA from a large, ethnically diverse cohort of obese or metabolically challenged youth. Results We confirmed 49 high-frequency variants, including a novel variant in the PDE11A gene (c.152C>T). Several other variants were associated with metabolic characteristics within ethnic groups. Discussion We conclude that a PKA pathway-specific variant search led to the identification of several new genetic associations with obesity in an ethnically diverse population.

الإتاحة: https://doi.org/10.3389/fendo.2023.1272939Test

المؤلفون: Bacha, Fida, El ghormli, Laure, Braffett, Barbara H., Shah, Amy S., Marcovina, Santica M., Levitt Katz, Lorraine E., Willi, Steven M., Caprio, Sonia, Dhaliwal, Ruban, Gidding, Samuel S.

المساهمون: National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases

المصدر: Diabetes Research and Clinical Practice ; volume 199, page 110671 ; ISSN 0168-8227

مصطلحات موضوعية: Endocrinology, General Medicine, Endocrinology, Diabetes and Metabolism, Internal Medicine

الإتاحة: https://doi.org/10.1016/j.diabres.2023.110671Test
https://api.elsevier.com/content/article/PII:S0168822723004321?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S0168822723004321?httpAccept=text/plainTest

المؤلفون: Tricò, Domenico, Chiriacò, Martina, Nouws, Jessica, Vash-Margita, Alla, Kursawe, Romy, Tarabra, Elena, Galderisi, Alfonso, Natali, Andrea, Giannini, Cosimo, Hellerstein, Marc, Ferrannini, Ele, Caprio, Sonia

المصدر: Diabetes; Jun2024, Vol. 73 Issue 6, p941-952, 12p

مصطلحات موضوعية: ADIPOSE tissues, CELL morphology, INSULIN, GLUCOSE intolerance, OBESITY

مستخلص: Excessive insulin secretion independent of insulin resistance, defined as primary hypersecretion, is associated with obesity and an unfavorable metabolic phenotype. We examined the characteristics of adipose tissue of youth with primary insulin hypersecretion and the longitudinal metabolic alterations influenced by the complex adipo-insular interplay. In a multiethnic cohort of adolescents with obesity but without diabetes, primary insulin hypersecretors had enhanced model-derived β-cell glucose sensitivity and rate sensitivity but worse glucose tolerance, despite similar demographics, adiposity, and insulin resistance measured by both oral glucose tolerance test and euglycemic-hyperinsulinemic clamp. Hypersecretors had greater intrahepatic and visceral fat depots at abdominal MRI, hypertrophic abdominal subcutaneous adipocytes, higher free fatty acid and leptin serum levels per fat mass, and faster in vivo lipid turnover assessed by a long-term ²H2O labeling protocol. At 2-year follow-up, hypersecretors had greater fat accrual and a threefold higher risk for abnormal glucose tolerance, while individuals with hypertrophic adipocytes or higher leptin levels showed enhanced β-cell glucose sensitivity. Primary insulin hypersecretion is associated with marked alterations in adipose tissue distribution, cellularity, and lipid dynamics, independent of whole-body adiposity and insulin resistance. Pathogenetic insight into the metabolic crosstalk between β-cell and adipocyte may help to identify individuals at risk for chronic hyperinsulinemia, body weight gain, and glucose intolerance. Article Highlights: Excessive insulin secretion independent of insulin resistance, named primary hypersecretion, has been associated with obesity and glucose intolerance. We examined whether early alterations in adipose tissue phenotype and function are linked to primary insulin hypersecretion in a complex interplay influencing glucose tolerance, β-cell function, and adiposity. In adolescents with obesity, insulin hypersecretors have greater ectopic fat depots, hypertrophic adipocytes, higher leptin and free fatty acid levels per fat mass, and greater lipid turnover than normosecretors. Hypertrophic adipocytes and hyperleptinemia predict short-term increases in β-cell glucose sensitivity, while the hypersecretory phenotype identifies individuals at risk of glucose intolerance and accruing adiposity over time. [ABSTRACT FROM AUTHOR]

: Copyright of Diabetes is the property of American Diabetes Association and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

المؤلفون: Vos, Miriam B, Abrams, Stephanie H, Barlow, Sarah E, Caprio, Sonia, Daniels, Stephen R, Kohli, Rohit, Mouzaki, Marialena, Sathya, Pushpa, Schwimmer, Jeffrey B, Sundaram, Shikha S, Xanthakos, Stavra A

المصدر: Journal of Pediatric Gastroenterology and Nutrition. 64(2)

مصطلحات موضوعية: Paediatrics, Biomedical and Clinical Sciences, Clinical Sciences, Nutrition and Dietetics, Pediatric, Chronic Liver Disease and Cirrhosis, Digestive Diseases, Health Services, Liver Disease, Hepatitis, Clinical Research, Oral and gastrointestinal, Good Health and Well Being, Bariatric Surgery, Child, Combined Modality Therapy, Diet Therapy, Exercise Therapy, Gastrointestinal Agents, Humans, Incidence, Non-alcoholic Fatty Liver Disease, Prevalence, Risk Factors, Severity of Illness Index, United States, children, nonalcoholic fatty liver disease, recommendations, treatment, Medical and Health Sciences, Gastroenterology & Hepatology, Clinical sciences, Nutrition and dietetics

الوصف: Nonalcoholic fatty liver disease (NAFLD) is a highly prevalent chronic liver disease that occurs in the setting of insulin resistance and increased adiposity. It has rapidly evolved into the most common liver disease seen in the pediatric population and is a management challenge for general pediatric practitioners, subspecialists and for health systems. In this guideline, the expert committee on NAFLD (ECON) reviewed and summarized the available literature, formulating recommendations to guide screening and clinical care of children with NAFLD.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/01f95498Test

المؤلفون: Slusher, Aaron L., Nouws, Jessica, Tokoglu, Fuyuze, Vash‐Margita, Alla, Matthews, Marcy D., Fitch, Mark, Shankaran, Mahalakshmi, Hellerstein, Marc K., Caprio, Sonia

المساهمون: Foundation for the National Institutes of Health, Robert E. Leet and Clara Guthrie Patterson Trust

المصدر: Obesity ; volume 32, issue 3, page 593-602 ; ISSN 1930-7381 1930-739X

الوصف: Objective The objective of this study was to examine the hypothesis that abdominal and gluteal adipocyte turnover, lipid dynamics, and fibrogenesis are dysregulated among insulin‐resistant (IR) compared with insulin‐sensitive (IS) adolescents with obesity. Methods Seven IS and seven IR adolescents with obesity participated in a 3‐h oral glucose tolerance test and a multi‐section magnetic resonance imaging scan of the abdominal region to examine body fat distribution patterns and liver fat content. An 8‐week 70% deuterated water ( 2 H 2 O) labeling protocol examined adipocyte turnover, lipid dynamics, and fibrogenesis in vivo from biopsied abdominal and gluteal fat. Results Abdominal and gluteal subcutaneous adipose tissue (SAT) turnover rates of lipid components were similar among IS and IR adolescents with obesity. However, the insoluble collagen (type I, subunit α2) isoform measured from abdominal, but not gluteal, SAT was elevated in IR compared with IS individuals. In addition, abdominal insoluble collagen Iα2 was associated with ratios of visceral‐to‐total (visceral adipose tissue + SAT) abdominal fat and whole‐body and adipose tissue insulin signaling, and it trended toward a positive association with liver fat content. Conclusions Altered extracellular matrix dynamics, but not expandability, potentially decreases abdominal SAT lipid storage capacity, contributing to the pathophysiological pathways linking adipose tissue and whole‐body IR with altered ectopic storage of lipids within the liver among IR adolescents with obesity.

الإتاحة: https://doi.org/10.1002/oby.23974Test

المؤلفون: Santos, Raul D., Wiegman, Albert, Caprio, Sonia, Cariou, Bertrand, Averna, Maurizio, Poulouin, Yann, Scemama, Michel, Manvelian, Garen, Garon, Genevieve, Daniels, Stephen

المصدر: JAMA Pediatrics ; volume 178, issue 3, page 283 ; ISSN 2168-6203

الوصف: Importance Many pediatric patients with heterozygous familial hypercholesterolemia (HeFH) cannot reach recommended low-density lipoprotein cholesterol (LDL-C) concentrations on statins alone and require adjunct lipid-lowering therapy (LLT); the use of alirocumab in pediatric patients requires evaluation. Objective To assess the efficacy of alirocumab in pediatric patients with inadequately controlled HeFH. Design, Setting, and Participants This was a phase 3, randomized clinical trial conducted between May 2018 and August 2022 at 43 centers in 24 countries. Pediatric patients aged 8 to 17 years with HeFH, LDL-C 130 mg/dL or greater, and receiving statins or other LLTs were included. Following consecutive enrollment into dosing cohorts, 25 of 99 patients screened for dosing every 2 weeks (Q2W) failed screening; 25 of 104 patients screened for dosing every 4 weeks (Q4W) failed screening. A total of 70 of 74 Q2W patients (95%) and 75 of 79 Q4W patients (95%) completed the double-blind period. Interventions Patients were randomized 2:1 to subcutaneous alirocumab or placebo and Q2W or Q4W. Dosage was based on weight (40 mg for Q2W or 150 mg for Q4W if <50 kg; 75 mg for Q2W or 300 mg for Q4W if ≥50 kg) and adjusted at week 12 if LDL-C was 110 mg/dL or greater at week 8. After the 24-week double-blind period, patients could receive alirocumab in an 80-week open-label period. Main Outcomes and Measures The primary end point was percent change in LDL-C from baseline to week 24 in each cohort. Results Among 153 patients randomized to receive alirocumab or placebo (mean [range] age, 12.9 [8-17] years; 87 [56.9%] female), alirocumab showed statistically significant reductions in LDL-C vs placebo in both cohorts at week 24. Least squares mean difference in percentage change from baseline was −43.3% (97.5% CI, −56.0 to −30.7; P < .001) Q2W and −33.8% (97.5% CI, −46.4 to −21.2; P < .001) Q4W. Hierarchical analysis of secondary efficacy end points demonstrated significant improvements in other ...

الإتاحة: https://doi.org/10.1001/jamapediatrics.2023.6477Test
https://jamanetwork.com/journals/jamapediatrics/articlepdf/2814614/jamapediatrics_santos_2024_oi_230095_1708531145.6393.pdfTest