NEUROGASTROENTEROLOGY

Ghrelin enhances gastric emptying in diabetic gastroparesis: a double blind, placebo controlled, crossover study

C D R Murray¹, N M Martin³, M Patterson³, S A Taylor², M A Ghatei³, M A Kamm¹, C Johnston⁴, S R Bloom³, A V Emmanuel¹

¹ Physiology Unit, St Mark’s Hospital, Harrow, Middlesex, UK
² Department of Radiology, St Mark’s Hospital, Harrow, Middlesex, UK
³ Department of Metabolic Medicine, Imperial College, Hammersmith Campus, London, UK
⁴ Department of Endocrinology, Hemel Hempstead Hospital, Hertfordshire, UK

Correspondence to:
Dr A V Emmanuel
Physiology Unit, St Mark’s Hospital, Harrow HA1 3UJ, UK; a.emmanuel{at}imperial.ac.uk

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

Methods: Ten insulin requiring diabetic patients (five men, six type I) referred with symptoms indicative of gastroparesis received a two hour infusion of either ghrelin (5 pmol/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 Clinic composite autonomic severity score (range 0 (normal)–3).

Results: Baseline ghrelin levels were mean 445 (SEM 36) pmol/l. Ghrelin infusion achieved a peak plasma level of 2786 (188) pmol/l at 90 minutes, corresponding to a peak GH of 70.9 (19.8) pmol/l. Ghrelin increased gastric emptying in seven of 10 patients (30 (6)% to 43 (5)%; p = 0.04). Impaired cardiovagal tone correlated inversely with peak postprandial 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.

Abbreviations: GH, growth hormone; GHS-R, growth hormone secretagogue receptor; PP, pancreatic polypeptide; CAN, cardiovagal autonomic neuropathy; GER, gastric emptying rate; BMI, body mass index; CASS, composite autonomic severity score

Keywords: ghrelin; diabetic gastroparesis; pancreatic polypeptide

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