Endocrine Abstracts

Aim: To assess the effects of a continuous overnight infusion of two doses of UAG (3&10 μg UAG/kg.hr-1) versus placebo in a double blind cross-over study on AG levels, as well on glucose and insulin response to a standard breakfast meal (SBM) in 8 overweight patients with type 2 diabetes (HbA1c 6.5-7.5%).

Methods: During these 3 admissions, in randomized order, all subjects received either placebo, or UAG 3 μg/kg.hr-1 or UAG 10 μg/kg.hr as a continuous venous infusion. The admission were divided by a wash-out period of >7 days. Serum glucose were assessed at regular intervals and via a continuous glucose monitor. Continuous infusion of either placebo or UAG started at 22.00 until 13.00 hr the next day. At 08.00–08.15 hr a standard breakfast meal (SBM) was used. SBM consisted out of 714 kcal (17% proteins; 46% fat; 37% carbohydrates).

Results: Morning AG levels (before SBM) dropped significantly from 21.01±8.9 (mean±SD) to 3.0±6.7, to 1.4±3.2 pg/ml after placebo, 3 and 10 mcg/kg.hr UAG infusion, respectively. After breakfast AG levels drop from 14.03±9.4, 0.8±1.8, to 0.8±1.8 pg/ml after placebo, 3 and 10 mcg/kg.hr-1 UAG infusion, respectively.

UAG levels, increased from 105.9±31.4, 10,998±2,623, 12,085±1,616 pg/ml after placebo, 3 and 10 mcg/kg.hr UAG infusion, respectively.

During continuous glucose monitoring, post-SBM, overnight infusion of 10 mcg/kg.hr UAG significantly decreased glucose levels. The AUC decreased from 1618, 1601, to 1540 mmol/3 hrs of placebo, 3 and 10 mcg UAG infusion.

A significant decrease in peak serum glucose levels after SBM during 10 mcg UAG infusion was observed.

Conclusion: UAG is a potent inhibitor of ghrelin levels in obese mild diabetics. Additionaly, UAG improves postprandial glycemia, especially in whom preprandial AG levels are high, which makes UAG (analogs) strong potential candidates for the development of drugs in the treatment of metabolic disorders or other conditions in which a disturbed AG/UAG ratio has been found.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.