{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T21:05:35Z","timestamp":1782335135642,"version":"3.54.5"},"reference-count":40,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2024,8,27]],"date-time":"2024-08-27T00:00:00Z","timestamp":1724716800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["dom-pubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Diabetes Obesity Metabolism"],"published-print":{"date-parts":[[2024,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>Diminished hepatic insulin clearance (HIC) is observed in obese adults and is presumed to be mediated by fatty liver. However, few reports have examined HIC in Chinese children with metabolic (dysfunction)\u2010associated fatty liver disease (MAFLD). This study aimed to investigate the correlation between HIC, insulin sensitivity and \u03b2\u2010cell function in obese Chinese children with MAFLD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In total, 204 obese children (74 MAFLD) aged 4\u201317\u2009years were enrolled into this study. HIC, insulin sensitivity and \u03b2\u2010cell function were calculated using the oral glucose tolerance test (1.75\u2009g\/kg body weight). Correlation analyses between the HIC and clinical variables were performed using Pearson's product\u2013moment correlation coefficients. HIC and glucose homeostasis were assessed in a high\u2010fat diet mouse model, and liver samples were collected for molecular analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Obese children with MAFLD exhibited significantly lower HIC (AUC\n                      <jats:sub>C\u2010peptide\/insulin ratio<\/jats:sub>\n                      ,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0019), higher insulin resistance (homeostatic model assessment of insulin resistance,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.002), and increased compensatory \u03b2\u2010cell function (homeostatic model assessment\u2010\u03b2,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.046) than obese children without liver involvement. Notably, HIC was negatively correlated with insulin sensitivity (\n                      <jats:italic>r<\/jats:italic>\n                      \u2009=\u2009\u22120.5035,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.0001) and \u03b2\u2010cell function (\n                      <jats:italic>r<\/jats:italic>\n                      \u2009=\u2009\u22120.4576,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.0001). However, pancreatic \u03b2\u2010cell dysfunction (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.046) was accompanied by future reduced HIC (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.034) in children with MAFLD in prediabetes. In a high\u2010fat diet mouse model, MAFLD mice showed a 50% reduction in insulin\u2010degrading enzyme expression, consistent with the observed decrease in HIC.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>A lower HIC may offload pancreatic \u03b2\u2010cells at an early stage. However, obese children with MAFLD are at risk of developing diabetes, and preventive efforts should be prioritized.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.15902","type":"journal-article","created":{"date-parts":[[2024,8,28]],"date-time":"2024-08-28T00:50:14Z","timestamp":1724806214000},"page":"5390-5398","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Reduced insulin clearance in paediatric metabolic (dysfunction)\u2010associated fatty liver disease and its dual role in beta\u2010cell offload and diabetes risk"],"prefix":"10.1111","volume":"26","author":[{"given":"Li","family":"Jiang","sequence":"first","affiliation":[{"name":"Department of Pediatric Endocrinology Affiliated Children's Hospital of Jiangnan University (Wuxi Children's Hospital)  Wuxi 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Wuxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sha","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Affiliated Women's Hospital of Jiangnan University (Wuxi Maternity and Child Health Care Hospital)  Wuxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lulian","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Pediatric Endocrinology Affiliated Children's Hospital of Jiangnan University (Wuxi Children's Hospital)  Wuxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-0588-0194","authenticated-orcid":false,"given":"Kerong","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pediatric Endocrinology Affiliated Children's Hospital of Jiangnan University (Wuxi Children's Hospital)  Wuxi 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