Heart failure patients often struggle with poor autonomic nervous system function, where the parasympathetic nerves fail to properly slow the heart after exercise, as measured by heart rate recovery at 60 seconds (HRR60) following cardiopulmonary testing. 
Metabolic issues like high glucose and insulin resistance commonly coexist with heart failure, but their specific impact on nerve recovery remains unclear. Researchers from the MyoVasc study, a prospective cohort, analyzed data from 1,588 fasting participants with a median age of 64 years, including 33% women and 43.7% with symptomatic heart failure. They examine how HbA1c, HOMA-IR (insulin resistance measure), and C-peptide relate to HRR60 both cross-sectionally and longitudinally over two years. The results were published in Cardiovascular Diabetology. 
Insulin Resistance Strongly Predicts Slow Heart Rate Recovery
In the full cohort with a median HRR60 of 21 beats per minute, higher HbA1c and HOMA-IR independently predicted worse HRR60 after adjustments, with beta coefficients per standard deviation of -0.074 (95% CI -0.122 to -0.026, P=0.003) for HbA1c and -0.113 (95% CI -0.165 to -0.062, P<0.0001) for HOMA-IR. When models included both glucose and insulin markers, HOMA-IR remained significant (beta -0.097, 95% CI -0.155 to -0.040, P<0.0001), while HbA1c lost strength (beta -0.030, P=0.28), indicating insulin resistance drives the effect more than average glucose levels. C-peptide showed the strongest link, with a beta of -0.171 (95% CI -0.225 to -0.117, P<0.0001) independent of HbA1c, persisting across heart failure and type 2 diabetes subgroups.
Long-Term Effects Confirm Insulin's Role Over Time
Longitudinal analysis over two years reinforced these findings, as higher baseline HbA1c (beta per SD -0.094, 95% CI -0.171 to -0.017, P=0.017) and C-peptide (beta -0.076, 95% CI -0.159 to 0.007, P=0.075) associated with slower HRR60 recovery, highlighting insulin status as a sustained predictor of autonomic dysfunction. This suggests that insulin dysregulation directly impairs vagal nerve reactivation after stress, beyond simple hyperglycemia, offering a new lens for heart failure risk assessment in metabolic patients.
Practical Steps for Heart Failure Management Teams
Clinicians managing heart failure patients with diabetes should routinely check insulin resistance markers like HOMA-IR or C-peptide alongside standard HbA1c, as these better predict autonomic recovery and guide therapy intensification with GLP-1 agonists or SGLT2 inhibitors that improve insulin sensitivity. For patient with poor exercise tolerance, poor HRR60 signals insulin-driven nerve issues, prompting metabolic optimization before advanced devices.
Future Research Targets Insulin-Nerve Pathways
These results call for mechanistic studies exploring how hyperinsulinemia disrupts parasympathetic signaling in heart failure, potentially leading to targeted interventions that restore vagal tone and improve outcomes.