AIMS: 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 (Delta) wake-up was defined as the difference between the maximum and minimum value during 1鈥痟 before and after wake-up time, before breakfast. RESULTS: Delta of low frequency/high frequency (LF/HF) around wake-up time (Delta LF/HF (wake-up)) was positively associated with Delta glucose (wake-up), standard deviation (SD) glucose (wake-up), the mean amplitude of glucose excursions (MAGE(24h)), and SD glucose(24h) after adjustment for age, sex, BMI, the duration of diabetes, and the prevalence of diabetic polyneuropathy (beta鈥?鈥?.47, p鈥?鈥?.011, beta鈥?鈥?.48, p鈥?鈥?.009, beta鈥?鈥?.54, p鈥?鈥?.002 and beta鈥?鈥?.41, p鈥?鈥?.0025, respectively). No association was found between Delta LF/HF(wake-up) and either mean blood glucose for 24鈥痟, 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.