Improved post-prandial ghrelin response by nateglinide or acarbose therapy contributes to glucose stability in Type 2 diabetic patients

Background: Recent studies highlight an important role of ghrelin in glucose homeostasis, while the association between ghrelin regulation and glucose fluctuation is unclear. Aim: We compared the effects of two postprandial hypoglycemic agents on ghrelin response and determined the contribution of ghrelin response to glucose stability in Type 2 diabetic (T2DM) patients. Subjects and methods: Forty newly-diagnosed T2DM patients were randomly allocated to receive nateglinide or acarbose for 4 weeks, with twenty body mass index (BMI)-matched normoglycemic subjects as controls. Mean glucose values and daily average glucose excursion were assessed using continuous glucose monitoring system. Serum ghrelin levels were determined by enzyme-linked immunosorbent assay. Results: T2DM patients had similar fasting ghrelin levels (p=0.546), while their postprandial ghrelin suppressions at 30 min and 120 min were reduced as corm pared to BMI-matched normoglycemic controls (p<0.01). Both nateglinide and acarbose increased post-prandial ghrelin suppression at 120 min and reduced ghrelin area under the curve (AUC(GHRL)) (p<0.05), while only nateglinide increased postprandial ghrelin suppression at 30 min (p<0.01), which was positively correlated with the increased early-phase insulin secretion by 4 weeks of nateglinide therapy (r=0.48, p=0.05). The decrease in AUC(GHRL) was positively correlated with the decrease in daily average glucose excursion and mean glucose values either by 4 weeks of nateglinide or acarbose therapy (p<0.05). Conclusions: Both nateglinide and acarbose increase post-prandial ghrelin suppression. Improved ghrelin regulation is most likely to play a role in glucose stability in T2DM patients with nateglinide or acarbose therapy. (C)2013, Editrice Kurtis