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
- 1Physiology Unit, St Mark’s Hospital, Harrow, Middlesex, UK
- 2Department of Radiology, St Mark’s Hospital, Harrow, Middlesex, UK
- 3Department of Metabolic Medicine, Imperial College, Hammersmith Campus, London, UK
- 4Department of Endocrinology, Hemel Hempstead Hospital, Hertfordshire, UK
- Correspondence to:
Dr A V Emmanuel
Physiology Unit, St Mark’s Hospital, Harrow HA1 3UJ, UK;
- Accepted 4 July 2005
- Revised 22 June 2005
- Published Online First 5 August 2005
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.
- 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
Published online first 5 August 2005
Conflict of interest: None declared.