{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T16:14:11Z","timestamp":1783440851819,"version":"3.54.6"},"reference-count":30,"publisher":"The Endocrine Society","issue":"10","license":[{"start":{"date-parts":[[2025,1,28]],"date-time":"2025-01-28T00:00:00Z","timestamp":1738022400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100003478","name":"Ministry of Health, Labour, and Welfare","doi-asserted-by":"publisher","award":["24FC1015"],"award-info":[{"award-number":["24FC1015"]}],"id":[{"id":"10.13039\/501100003478","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,9,16]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>Type A insulin resistance syndrome (IRS), characterized by impaired insulin receptor function due to variants of the insulin receptor gene, manifests as severe insulin-resistant diabetes. Differentiation of type A IRS from type 2 diabetes on the basis of hyperinsulinemia can be challenging. Given the association between insulin receptor dysfunction and reduced insulin clearance, we evaluated the potential of the circulating C-peptide reactivity (CPR)\/immunoreactive insulin (IRI) molar ratio, a marker of insulin clearance, for distinguishing type A IRS from type 2 diabetes.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We retrospectively analyzed CPR and IRI levels measured during a 75-g oral glucose tolerance test (OGTT) in 18 individuals with type A IRS and 126 with type 2 diabetes. Receiver operating characteristic (ROC) curve analysis was performed to determine the diagnostic performance of the CPR\/IRI molar ratio and IRI levels.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>IRI levels were significantly higher and the CPR\/IRI molar ratio significantly lower in individuals with type A IRS compared with those with type 2 diabetes. The area under the ROC curve for the CPR\/IRI molar ratio at baseline, 1 hour, and 2 hours after OGTT initiation was 0.997 (sensitivity 100%, specificity 99.2%), 0.999 (sensitivity 100%, specificity 97.6%), and 0.997 (sensitivity 100%, specificity 95.1%), respectively. The CPR\/IRI molar ratio demonstrated robust diagnostic performance regardless of body mass index or hyperinsulinemia severity.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>The CPR\/IRI molar ratio, both at baseline and during OGTT, exhibited higher sensitivity and specificity than IRI levels alone for distinguishing type A IRS from type 2 diabetes. This ratio may serve as a reliable clinical marker for early and accurate diagnosis of type A IRS.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1210\/clinem\/dgaf043","type":"journal-article","created":{"date-parts":[[2025,1,24]],"date-time":"2025-01-24T15:20:19Z","timestamp":1737732019000},"page":"e3383-e3390","source":"Crossref","is-referenced-by-count":5,"title":["Utility of the C-Peptide\/Insulin Molar Ratio for Distinguishing Type A Insulin Resistance Syndrome From Type 2 Diabetes"],"prefix":"10.1210","volume":"110","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-4348-6118","authenticated-orcid":false,"given":"Seiji","family":"Nishikage","sequence":"first","affiliation":[{"name":"Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine , Kobe 650-0017 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3035-4155","authenticated-orcid":false,"given":"Yushi","family":"Hirota","sequence":"additional","affiliation":[{"name":"Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine , Kobe 650-0017 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-8781-2725","authenticated-orcid":false,"given":"Tomofumi","family":"Takayoshi","sequence":"additional","affiliation":[{"name":"Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine , Kobe 650-0017 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-6144-1320","authenticated-orcid":false,"given":"Kai","family":"Yoshimura","sequence":"additional","affiliation":[{"name":"Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine , Kobe 650-0017 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takehito","family":"Takeuchi","sequence":"additional","affiliation":[{"name":"Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine , Kobe 650-0017 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetsushi","family":"Hamaguchi","sequence":"additional","affiliation":[{"name":"Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine , Kobe 650-0017 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariko","family":"Ueda","sequence":"additional","affiliation":[{"name":"Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine , Kobe 650-0017 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-3672-2809","authenticated-orcid":false,"given":"Akane","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine , Kobe 650-0017 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1577-2401","authenticated-orcid":false,"given":"Kazuhiko","family":"Sakaguchi","sequence":"additional","affiliation":[{"name":"Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine , Kobe 650-0017 ,","place":["Japan"]},{"name":"Division of General Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine , Kobe 650-0017 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0432-4366","authenticated-orcid":false,"given":"Wataru","family":"Ogawa","sequence":"additional","affiliation":[{"name":"Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine , Kobe 650-0017 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2025,1,28]]},"reference":[{"issue":"14","key":"2025091917014525400_dgaf043-B1","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1056\/NEJM197604012941401","article-title":"The syndromes of insulin resistance and acanthosis nigricans. 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