OBJECTIVE : It is known that autonomic nerve activity (ANA) affects glucose metabolism by regulating the secretion of insulin and glucagon. Sympathetic nerve stimulation results in increased blood glucose levels. ANA also showed a circadian variation, and sympathetic nerve activity was minimal at night and began to rise at arousal. Therefore, a drastic alteration in ANA around wake-up would be associated with glycemic variability (GV) known risk factor for cardiovascular disease. We investigated the relation between ANA around wake-up and either morning or daily GV. METHODS : We simultaneously performed Holter ECG and continuous glucose monitoring system in 41 patients with type 2 diabetes (T2D). ANA was assessed by heart rate variability (HRV) analysis. Delta (Δ) wake-up was defined as the difference between the maximum and minimum value during 1 h before and after wake-up time, before breakfast. RESULTS : Δ of low frequency/high frequency (LF/HF) around wake-up time (Δ LF/HF wake-up) was positively associated with Δ glucose wake-up, standard deviation (SD) glucose wake-up, the mean amplitude of glucose excursions (MAGE24h), and SD glucose24h after adjustment for age, sex, BMI, the duration of diabetes, and the prevalence of diabetic polyneuropathy (β = 0.47, p = 0.011, β = 0.48, p = 0.009, β = 0.54, p = 0.002 and β = 0.41, p = 0.0025, respectively). No association was found between Δ LF/HFwake-up and either mean blood glucose for 24 h, or HbA1c as parameters of chronic hyperglycemia. CONCLUSIONS : In T2D, the fluctuation in fasting sympathetic nerve activity around wake-up was positively associated with not only morning but also daily GV.