Metabolic Syndrome (MetS) is associated with autonomic cardiac dysregulation, reflected by changes in heart rate variability (HRV) and detrimental effects on kidney function. This study aimed to 1) compare metabolic factors and hormones, kidney function profiles, and HRV parameters, including SDSD, RMSSD, pNN50, high-frequency power (HF), low-frequency power (LF), LF/HF ratio, between subjects with/without MetS or insulin resistance and 2) determine the correlations among these variables. We hypothesized that these factors differed between subjects with and without metabolic disturbances. Furthermore, we expected that metabolic factors and hormones and kidney function parameters were associated with HRV. In Thai obese subjects, characterized by BMI ≥ 25 kg/m2 for an Asian population (n = 45), fasting blood samples and spontaneous 5-minute HRV were obtained. The criteria for MetS were defined by The NCEP ATP III 2005 definition, except waist circumference which is ≥ 90 cm in men and 80 cm in women for Asians. Insulin resistance was determined by homeostatic model assessment for insulin resistance (HOMA-IR) > 2.3. In subjects with MetS (n = 19), percent fat, HOMA-IR, and serum leptin were significantly higher than those without MetS (n = 26), all with P < 0.05. Serum adiponectin, SDSD, RMSSD, and LF in ms2 tended to decrease in subjects with MetS. In subjects with insulin resistance (n = 30), BMI and serum leptin were significantly higher than those without insulin resistance (n = 15), all with P < 0.05. HDL-cholesterol (HDL-C) was significantly lower in subjects with insulin resistance, all with P < 0.05. Serum leptin exhibited positive correlations with BMI, creatinine clearance (CrCl), serum insulin, and HOMA-IR (R = 0.433-0.778) but had a negative correlation with HDL-C (R = -0.303), all with P < 0.05. Serum insulin showed positive correlations with BMI, CrCl, and serum leptin (R = 0.328-0.437); while it had negative correlations with age and HDL-C (R = (-0.310)-(-0.438)), all with P < 0.05. Serum adiponectin demonstrated positive correlations with HDL-C and pNN50 (R = 0.329-0.473), all with P < 0.05. CrCl had positive correlations with BMI, HOMA-IR, serum insulin and leptin, and HF in normal unit (nu) (R = 0.304-0.617); and negative correlations with LFnu, and LF/HF ratio (R = (-0.317)-(-0.386)), all with P < 0.05. HDL-C demonstrated significant positive correlations with serum adiponectin, SDSD, and RMSSD (R = 0.329-0.331); while showed negative correlations with the number of criteria met for MetS, BMI, triglyceride, serum insulin and leptin, and HOMA-IR (P = (-0.303)-(-0.595)), all with P < 0.05. LDL-cholesterol (LDL-C) had negative correlations with percent fat and pNN50 (R = (-0.313)-(-0.340)), all with P < 0.05. Subjects with metabolic syndrome tended to have decreased insulin sensitivity, serum adiponectin, as well as parasympathetic (SDSD, RMSSD) and sympathetic (LF) HRV. Those with insulin resistance showed lower level of HDL-C. Leptin and insulin were correlated with obesity, metabolic factors, insulin resistance, and kidney function parameters but not HRV. Interestingly, serum adiponectin exhibited a positive correlation with HDL-C, and both serum adiponectin and HDL-C, which are protective factors, had positive correlations with parasympathetic HRV (pNN50, SDSD, and/or RMSSD). Conversely, LDL-C showed a negative correlation with parasympathetic HRV (pNN50). Creatinine clearance was positively correlated with parasympathetic HRV (HF) and negatively correlated with sympathetic HRV (LFnu and LF/HF ratio). In conclusion, MetS was linked to shifts in HRV, with reductions in both parasympathetic and sympathetic components. HDL-C exhibited a protective role in metabolic disturbances. Parasympathetic HRV was positively correlated with protective factors but negatively with LDL-C. Deteriorating kidney function was associated with increased sympathetic HRV and decreased parasympathetic HRV. The research was funded by the Faculty of Medicine Siriraj Hospital Research Fund ((IO) R015932003, R0159333013 and R016132012. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.