METABOLIC PREDICTORS OF CARDIAC AUTONOMIC NEUROPATHY IN TYPE 2 DIABETES: ASSOCIATIONS OF GLYCEMIC CONTROL, LIPID FRACTIONS, AND RENAL MARKERS WITH AUTONOMIC DYSFUNCTION

Background: Cardiac autonomic neuropathy (CAN) represents one of the most overlooked yet clinically consequential complications of type 2 diabetes mellitus (T2DM), as it predisposes patients to heightened cardiovascular risk and contributes substantially to early mortality. While cardiovascular autonomic reflex tests (CARTs) provide standardized diagnostic tools, the metabolic determinants of CAN remain incompletely elucidated. Objective: This study aimed to identify glycemic, lipid, and renal predictors of CAN and to determine their associations with CART-derived indices in Iraqi patients with T2DM. Methods: A case–control study was conducted in Mosul, Iraq, between October 2024 and January 2025, enrolling 100 patients with T2DM (≥5 years duration) and 100 age- and sex-matched controls. Clinical data, anthropometry, glycemic markers (HbA1c, fasting plasma glucose), lipid profile (TC, TG, HDL-C, LDL-C, VLDL-C), and renal function (urea, creatinine, proteinuria) were measured using standardized laboratory methods. Autonomic function was assessed via CARTs (Valsalva, E/I, and 30:15 ratios). Associations were analyzed using correlations, multivariable regression, and mediation analysis. Results: CAN was detected in 82.5% of participants, with 40.0% classified as early and 42.5% as definite. HbA1c, TC, TG, LDL-C, VLDL-C, creatinine and serum urea increased progressively with CAN severity (p < 0.0001). CART indices (E/I and 30:15 ratios) declined stepwise across severity groups. Multivariable analysis identified HbA1c, TG, and urea as independent predictors of CAN severity, and mediation modeling suggested that lipid fractions partially mediated the effect of hyperglycemia on autonomic impairment. Receiver operating characteristic (ROC) analysis revealed acceptable discriminatory ability of HbA1c, triglycerides, and urea for definite CAN, with combined models outperforming individual predictors. Conclusion: CAN is highly prevalent among Iraqi patients with T2DM and is strongly associated with poor glycemic control, dyslipidemia, and subtle renal dysfunction. Integrating these metabolic indices may provide an early biochemical signature of CAN risk, underscoring the need for targeted screening and preventive strategies.