March 3, 2026Open Access

Nonlinear HbA1c thresholds reveal accelerated atherogenic remodeling and improved risk reclassification in type 2 diabetes

Key Points

Accelerated atherogenic remodeling occurs at HbA1c thresholds of 8.0%-8.5%, linked to cardiovascular disease risk.
The study identifies triglyceride-to-HDL cholesterol ratio mediating 56.9% of the effect of HbA1c on atherogenic index.

Structured PICO

Do specific HbA1c thresholds and the Atherogenic Index of Plasma (AIP) improve cardiovascular risk reclassification in adults with type 2 diabetes not on lipid-lowering therapy?

Population

271 adults with type 2 diabetes not receiving lipid-lowering therapy

Intervention

HbA1c levels (good <7.0%, moderate 7.0%-8.49%, poor ≥8.5%)

Comparator

Comparisons across different HbA1c control groups

Outcome

Atherogenic lipid burden (evaluated using Atherogenic Index of Plasma [AIP], Castelli indices, TG/HDL-C, non-HDL cholesterol, and remnant cholesterol) and cardiovascular risk reclassification (Net Reclassification Improvement [NRI])surrogate

An HbA1c of 8.0%-8.5% represents a metabolically vulnerable threshold for accelerated atherogenic dyslipidemia in type 2 diabetes, where adding the Atherogenic Index of Plasma improves cardiovascular risk reclassification.

Abstract

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) -a surrogate of insulin-resistance-related lipid metabolism-and assess the incremental predictive value of the Atherogenic Index of Plasma (AIP) within the clinically ambiguous "glycemic gray zone. " A total of 271 adults with T2D not receiving lipid-lowering therapy were retrospectively grouped by HbA1c: good (NRI) tested the added predictive value of AIP over conventional lipid markers. All atherogenic indices worsened with deteriorating glycemia (p < 0. 001). Non-linear inflection points were observed at HbA1c 8. 0% for TG/HDL-C and 8. 5% for AIP (pₙon-linearity < 0. 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%-8. 5% transition range (categorical NRI = 0. 384; 95% CI: 0. 184-0. 584). These findings identify 8. 0%-8. 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.

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