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. We measured three point PGs by Point-of-Care Testing (POCT) and flash glucose monitoring system (FreeStyle Libre Pro™); midnight (3 am), the time of awakening (about 6 am) and just before breakfast (8 am), hormones and their metabolites in 32 hospitalized patients with type 2 diabetes. Those with insulin therapy or overtly elevated fasting PG (>11 mmol/L) were excluded. W1 could be explained by relative insulin deficiency. Urinary normetanephrine, reflects a sum of production of norepinephrine was significantly correlated with W2 (R=0.422, p<0.01). Level of other antagonistic hormones including urinary metanephrine was not correlated with W2. Norepinephrine, a relatively selective agonist of alpha-adrenergic receptor, within the normal range, may be responsible for W2. It has been reported that spironolactone, a nonselective mineralocorticoid receptor antagonist, may have a deleterious effect on glycemia. Spironolactone (25mg) was administered 5 female diabetic patients with hypertension for seven days. Spironolactone significantly increased W2 (8 am PG minus 6 am PG) (0.1±0.4 mmol/L to 0.5±0.9 mmol/L, p<0.05) but not W1(6 am PG minus 3 am PG) (0.2±0.5 mmol/L to 0.2±0.3 mmol/L, p>0.05). The Urinary normetanephrine was increased by the treatment (0.19±0.19 mg/gCre to 0.26±0.11 mg/gCre, p<0.05). But the treatment did not change urinary metanephrine (0.16±0.10 mg/gCre to 0.17±0.08 mg/gCre, p>0.05). Further, eplerenone(50mg), a selective mineralocorticoid receptor antagonist affected neither W1 nor W2 in 2 male diabetes patients with hypertension. These results suggested that nonselective mineralocorticoid receptor antagonist may affect glucose metabolism via change of alpha-adrenergic tone.


K. Yamauchi: None.

Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at