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Aims/Introduction: Diabetic cardiovascular autonomic neuropathy (DCAN) seriously threatens the prognosis and quality of life of patients with type 2 diabetes mellitus, associated with increased mortality. The present study aimed to investigate the relevant risk factors of DCAN. Materials and Methods: The present study enrolled a total of 109 patients with type 2 diabetes mellitus. DCAN was defined as a score of at least 2 points in Ewing tests. The updated homeostasis model assessment of insulin resistance (HOMA2‐IR) based on fasting C‐peptide was calculated to reflect insulin resistance. Logistic regression analysis, interaction and stratified analyses were used to investigate the relationship between HOMA2‐IR or other indicators and DCAN. Receiver operating characteristic analysis was carried out to estimate the discriminative value of the variables independently associated with DCAN and to determine the optimal cut‐off point of these models to screen DCAN. Results: The HOMA2‐IR levels were significantly higher in patients with DCAN, and tended to be worsened with the progression of the DCAN. Logistic regression analysis showed an independent association between HOMA2‐IR (odds ratio 39.30, 95% confidence interval 7.17–215.47) and DCAN. HOMA2‐IR (area under the curve 0.878, 95% confidence interval 0.810–0.946; cut‐off value 1.735) individually predicted DCAN significantly higher than the other independent risk factors individually used, whereas models combining HOMA2‐IR and other risk factors did not significantly boost the diagnostic power. Conclusions: Insulin resistance is independently associated with DCAN. HOMA2‐IR presents to be a highly accurate and parsimonious indicator for DCAN screening. Patients with HOMA2‐IR >1.735 are at a high risk of DCAN; thus, priority diagnostic tests should be carried out for these patients for timely integrated intervention. [ABSTRACT FROM AUTHOR]