Previously, we reported that morning plasma glucose (PG) elevation before wake-up (W1) and after wake-up (W2), occur through different mechanisms in patients with type 2 diabetes. W1 was related to insulin deficiency as already-known reports. W2 could be explained by heightened ambient alpha-adrenergic tone, within the normal range since urinary normetanephrine was strongly related to W2. Urinary normetanephrine are reflected production levels of norepinephrine. Although epinephrine activates both of α and β adrenergic receptors, norepinephrine only stimulates α adrenergic receptor. In the study, we estimate the effect of SGLT2 inhibitors on urinary metanephrines, other antagonistic hormones and W2. Ipragliflozin (50mg) or dapagliflozin (5mg) administered 8 diabetic patients with W2 for 3 month. Those with insulin therapy or overtly elevated fasting PG (>11 mmol/L) were excluded. SGLT2 inhibitors suppressed δPG(8 am PG minus 6 am PG) (2.7±1.1 mmol/L to 1.9±0.9 mmol/L, p<0.05)(Figure) and urinary normetanephrine(0.27±0.19 mg/gCre to 0.20±0.11 mg/gCre, p<0.05). But those did not change urinary metanephrine(0.19±0.10 mg/gCre to 0.17±, p>0.05) and other antagonistic hormones. Adrenergic tone-induced alterations of glucose metabolism may be mediated via regulation of SGLT2 inhibitor.


K. Yamauchi: None.

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