Ghrelin enhances gastric emptying in diabetic gastroparesis: a double-blind, placebo-controlled, cross- over study

Charles D.R Murray ^1*, Niamh M Martin ², Michael Patterson ², Stuart Taylor ¹, Mohammad A Ghatei ², Michael A Kamm ¹, Colin Johnston ³, Stephen R Bloom ² and Anton V Emmanuel ¹

¹ St Mark's Hospital, United Kingdom
² Department of Metabolic Medicine, Hammersmith Hospital, United Kingdom
³ Department of Endocrinology, Hemel Hempstead Hospital, United Kingdom

^* To whom correspondence should be addressed. E-mail: charlie.murray{at}talk21.com.

Accepted 4 July 2005

Abstract

Background: Diabetic gastroparesis is a disabling condition with no consistently effective treatment. In animals, ghrelin increases gastric emptying and reverses post-operative ileus. We present the results of a double- blind placebo-controlled cross-over study of ghrelin in gastric emptying in patients with diabetic gastroparesis.

Methods: Ten insulin requiring diabetic patients (5 men, 6 Type I) referred with symptoms indicative of gastroparesis received a two hour infusion of either ghrelin (5pmol/kg/min) or saline on two occasions. Blood glucose was controlled by euglycaemic clamp. Gastric emptying rate (GER) was calculated by real-time ultrasound following a test meal. Blood was sampled for ghrelin, growth hormone (GH) and pancreatic polypeptide (PP) levels. Cardiovagal neuropathy was assessed using the Mayo CASS scale [range 0(normal)-3].

Results: Baseline ghrelin levels were 445± 36 pmol/l (mean±SEM). Ghrelin infusion achieved a peak plasma level of 2786±188 pmol/l at 90 minutes, corresponding with a peak GH of 70.9± 19.8 pmol/l. Ghrelin increased gastric emptying in seven of ten patients (30±6% to 43±5%, p=0.04). Impaired cardiovagal tone correlated inversely with peak post-prandial PP values (p<0.05), but did not correlate with GER.

Conclusions: Ghrelin increases gastric emptying in patients with diabetic gastroparesis. This is independent of vagal tone. We propose that analogues of ghrelin may represent a new class of prokinetic agents.

Keywords: diabetic gastroparesis, gastric emptying, ghrelin, pancreatic polypeptide

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