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.
