{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T16:18:18Z","timestamp":1787761098173,"version":"build-2784847793"},"reference-count":26,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T00:00:00Z","timestamp":1769731200000},"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. Cardiovasc. Med."],"abstract":"<jats:p>\n                    Dysglycemia, lipid metabolism, and cardiovascular disease (CVD) progression in type 2 diabetes (T2D) are closely interconnected, yet the non-linear lipid remodeling processes underlying atherogenic dyslipidemia remain insufficiently defined. This study aimed to identify HbA1c thresholds associated with accelerated lipid-driven atherogenesis, quantify the mediating role of the triglyceride-to-HDL cholesterol ratio (TG\/HDL-C)\u2014a surrogate of insulin-resistance\u2013related lipid metabolism\u2014and assess the incremental predictive value of the Atherogenic Index of Plasma (AIP) within the clinically ambiguous \u201cglycemic gray zone.\u201d A total of 271 adults with T2D not receiving lipid-lowering therapy were retrospectively grouped by HbA1c: good (&amp;lt;7.0%), moderate (7.0%\u20138.49%), and poor (\u22658.5%) control. Atherogenic lipid burden was evaluated using AIP, Castelli indices, TG\/HDL-C, non-HDL cholesterol, and remnant cholesterol. Restricted cubic splines were used to explore non-linear HbA1c\u2013lipid relationships; mediation analysis estimated the TG\/HDL-C contribution to the HbA1c\u2013AIP pathway; and Net Reclassification Improvement (\n                    <jats:italic>N<\/jats:italic>\n                    RI) tested the added predictive value of AIP over conventional lipid markers. All atherogenic indices worsened with deteriorating glycemia (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&amp;lt;\u20090.001). Non-linear inflection points were observed at HbA1c 8.0% for TG\/HDL-C and 8.5% for AIP (p_non-linearity\u2009&amp;lt;\u20090.01). TG\/HDL-C mediated 56.9% of the HbA1c effect on AIP, indicating its central role in linking hyperglycemia to lipid remodeling. Adding AIP improved cardiovascular risk reclassification, particularly in the 8.0%\u20138.5% transition range (categorical NRI\u2009=\u20090.384; 95% CI: 0.184\u20130.584). These findings identify 8.0%\u20138.5% as a metabolically vulnerable HbA1c threshold marked by accelerated atherogenic dyslipidemia. AIP functions as a sensitive lipid-based marker for cardiometabolic risk detection within this gray zone, while TG\/HDL-C acts as a key mechanistic mediator, supporting the integration of atherogenic lipid indices into individualized risk assessment and precision lipid management strategies in T2D.\n                  <\/jats:p>","DOI":"10.3389\/fcvm.2026.1751404","type":"journal-article","created":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T06:41:49Z","timestamp":1769755309000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Nonlinear HbA1c thresholds reveal accelerated atherogenic remodeling and improved risk reclassification in type 2 diabetes"],"prefix":"10.3389","volume":"13","author":[{"given":"Vehbi","family":"\u015eirik\u00e7i","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H\u00fcseyin 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