Different Relationship Between Glycemic Status and Autonomic Function in Patients with Type 2 Diabetes Mellitus and in Healthy Controls

Autonomic neuropathy is a common complication in diabetes mellitus (DM). Decreased vagal nerve activity and augmented sympathetic nerve activity have been reported in patients with DM. However, the relationship between autonomic function and glycemic status in DM and in individuals without DM remains unclear. We hypothesized that indices of sympathetic and vagal nerve activity are related to glycemic status. Eleven patients who were clinically diagnosed with type-2 DM (HbA1c, 6.8 ± 0.3%; age, 54 ± 3 yrs), and 20 healthy non-DM individuals (including 10 pre-DM; HbA1c < 6.5%; range 5.1-6.1%; age, 59 ± 2 yrs) were studied (19 male, 12 female). Five DM patients had hypertension. Patients with DM and hypertensives were treated with standard medications. Beat-by-beat blood pressure (BP), heart rate (HR) and muscle sympathetic nerve activity (MSNA) were recorded under resting conditions. HR variability (HRV) was calculated and spontaneous cardiovagal baroreflex sensitivity (CBRS) was evaluated with the sequence method. CBRS in DM was lower than in non-DM subjects (P < 0.05). MSNA in DM was also lower than in non-DM subjects (P < 0.05). In linear regression analyses with data from all subjects, CBRS was negatively correlated with fasting blood glucose (FBG) (R = -0.47), insulin (R = -0.42), and homeostasis model assessment of insulin resistance (HOMA-IR) (R = -0.43) (P < 0.05 for all). MSNA was negatively correlated with HbA1c and HOMA-IR (R = -0.41, -0.42, respectively; both, P < 0.05). The high frequency (HF) component of HRV (i.e., an index of vagal tone) was negatively correlated with insulin (R = -0.46) and HOMA-IR (R = -0.42) in all subjects (P < 0.05 for both). In non-DM subjects, CBRS was negatively correlated with FBG (R = -0.53, P <0.05). HF was negatively correlated with FBG (R = -0.51), insulin (R = -0.66), and HOMA-IR (R = -0.66) (P < 0.05 for all), but MSNA was not correlated with glycemic/insulin status in non-DM subjects. Whereas in DM patients, MSNA tended to be negatively correlated with HOMA-IR (R = -0.77, P = 0.07). In the present study, both MSNA and vagal activity (CBRS and HF) were decreased in relation to the glycemic/insulin status. Vagal nerve activity was associated with the glycemic/insulin status even in non-DM subjects (i.e., healthy and pre-DM). Based on these results, we speculate that both vagal and sympathetic nerves were injured by DM progression, and that vagal neuropathy preceded the sympathetic neuropathy. Our results differ from prior reports that showed that MSNA in DM was higher than in non-DM. However, in our study subjects, the severity of DM was mild, and except for hypertension in 5 subjects, none had manifestations of diabetic end-organ damage. Differences in the duration and severity of DM as well as the effects of the treatments could contribute to the differences in the results. Further studies on the autonomic function during the DM progression are warranted. © FASEB.