{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T06:18:48Z","timestamp":1787811528564,"version":"build-2784847793"},"reference-count":22,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T00:00:00Z","timestamp":1787788800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The global epidemic of type 2 diabetes mellitus (T2D), along with its rising prevalence among younger populations, raises substantial public health concerns; severe hypertriglyceridemia (sHTG) is a major risk factor for acute pancreatitis. Insulin resistance in T2D often coincides with dyslipidemia, contributing to lipotoxicity, and insulin-resistant states may be linked to specific genetic variants.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Case presentation<\/jats:title>\n                    <jats:p>\n                      This report presents a 27-year-old man with poor glycemic control, recurrent dizziness, extreme hypertriglyceridemia (TG &amp;gt; 37.87 mmol\/L), insulin resistance, pancreatic fat infiltration, and early-stage diabetic nephropathy. Despite a family history of T2D, his clinical presentation far exceeded that of typical T2D. High-throughput sequencing revealed a heterozygous\n                      <jats:italic>LRP6<\/jats:italic>\n                      variant (c.3107A&amp;gt;G, p.Asn1036Ser).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Outcome<\/jats:title>\n                    <jats:p>Multidisciplinary treatment\u2014incorporating acute-phase plasma exchange, \u03c9-3 fatty acid ethyl ester 90, inclisiran, subcutaneous insulin aspart pump therapy, metformin, insulin icodec, finerenone, and Huangkui capsules\u2014led to improvements in the patient\u2019s metabolic indicators.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance<\/jats:title>\n                    <jats:p>\n                      This case report describes a patient with type 2 diabetes mellitus presenting with extreme metabolic disorders, in whom a variant in the\n                      <jats:italic>LRP6<\/jats:italic>\n                      gene was detected. Although the variant co-occurs with the observed phenotype, its pathogenicity cannot currently be established in the absence of functional validation. This case emphasizes that genetic variant screening should be considered in patients with unexplained severe metabolic disturbances, particularly those with early-onset disease. This case also provides a foundation for future functional studies and genetic confirmation.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2026.1887705","type":"journal-article","created":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T05:39:48Z","timestamp":1787809188000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["A case report of young-onset type 2 diabetes patient with severe metabolic dysregulation carrying an LRP6 variant"],"prefix":"10.3389","volume":"17","author":[{"given":"Dan","family":"Xiang","sequence":"first","affiliation":[{"name":"Department of Endocrinology, Taikang Xianlin Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University","place":["Nanjing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Taikang Xianlin Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University","place":["Nanjing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuaiju","family":"Liao","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Taikang Xianlin Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University","place":["Nanjing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yangtian","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Taikang Xianlin Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University","place":["Nanjing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,27]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(22)01655-5","article-title":"Type 2 diabetes","volume":"400","author":"Ahmad","year":"2022","journal-title":"Lancet"},{"key":"B2","doi-asserted-by":"publisher","first-page":"12","DOI":"10.7573\/dic.2023-6-1","article-title":"Tirzepatide for type 2 diabetes","volume":"22","author":"Anderson","year":"2023","journal-title":"Drugs Context"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2023.108544","article-title":"Severe hypertriglyceridemia: existing and emerging therapies","volume":"251","author":"Malick","year":"2023","journal-title":"Pharmacol Ther"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22168590","article-title":"Insulin signal transduction perturbations in insulin resistance","volume":"22","author":"Khalid","year":"2021","journal-title":"Int J Mol Sci"},{"key":"B5","doi-asserted-by":"publisher","first-page":"19","DOI":"10.3389\/fimmu.2021.727008","article-title":"Type 2 innate lymphoid cells: protectors in type 2 diabetes","volume":"12","author":"Painter","year":"2021","journal-title":"Front Immunol"},{"key":"B6","doi-asserted-by":"publisher","first-page":"17","DOI":"10.2147\/DMSO.S397643","article-title":"Pathophysiological mechanisms and clinical associations of non-alcoholic fatty pancreas disease","volume":"22","author":"Pagkali","year":"2024","journal-title":"Diabetes Metab Syndr Obes"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1007\/BF00280883","article-title":"Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man","volume":"28","author":"Matthews","year":"1985","journal-title":"Diabetologia"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.27.6.1487","article-title":"Use and abuse of HOMA modeling","volume":"27","author":"Wallace","year":"2004","journal-title":"Diabetes Care"},{"key":"B9","doi-asserted-by":"publisher","first-page":"795","DOI":"10.1016\/j.pan.2020.06.005","article-title":"Hypertriglyceridemia and acute pancreatitis","volume":"20","author":"Yang","year":"2020","journal-title":"Pancreatology"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.4103\/ijem.ijem_206_22","article-title":"Hypertriglyceridemia-induced acute pancreatitis - 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