OBJECTIVE: It is unclear to which extent altered insulin sensitivity/secretion contribute to the development of diabetic cardiovascular autonomic neuropathy (CAN) characterized by diminished heart rate variability (HRV). We hypothesised that lower HRV is differentially associated with measures of insulin resistance and insulin secretion in recent-onset type 1 and type 2 diabetes. MATERIALS/METHODS: This cross-sectional study included participants from the German Diabetes Study with type 1 (n=275) or type 2 diabetes (n=450) with known diabetes duration </=1year and glucose-tolerant controls (n=81). Four time domain and frequency domain HRV measures each, reflecting vagal and/or sympathetic modulation were determined over 3h during a hyperinsulinaemic-euglycaemic clamp. Insulin sensitivity was calculated as the M-value, while insulin secretion was determined by glucagon-stimulated incremental C-peptide (DeltaC-peptide). RESULTS: After adjustment for sex, age, BMI, smoking, and HbA1c, both M-value and DeltaC-peptide were lower in the diabetes groups compared to controls (P<0.05). In multiple linear regression analyses after Bonferroni correction, vagus-mediated HRV indices were positively associated with M-value in both diabetes types (P<0.05) and inversely associated with DeltaC-peptide only in participants with type 1 diabetes (P<0.05). In type 2 diabetes, the low-frequency/high-frequency (LF/HF) power as an indicator of sympathovagal balance was weakly inversely associated with M-value. CONCLUSIONS: Insulin resistance may contribute to the development of early cardiovagal suppression rather than sympathetic predominance in both diabetes types, while in type 1 diabetes a lower glucagon-stimulated insulin secretion is linked to a possibly compensatory higher parasympathetic tone. Whether interventions aimed at reducing insulin resistance could also reduce the risk of CAN remains to be established.