Ghrelin enhances gastric emptying in diabetic gastroparesis: a double blind, placebo controlled, crossover study.
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.
Murray
C D R
CD
Physiology Unit, St Mark's Hospital, Harrow HA1 3UJ, UK.
Martin
N M
NM
Patterson
M
M
Taylor
S A
SA
Ghatei
M A
MA
Kamm
M A
MA
Johnston
C
C
Bloom
S R
SR
Emmanuel
A V
AV
D000328:Adult; D018592:Cross-Over Studies; D048909:Diabetes Complications / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D005746:Gastric Emptying / Q000187:drug effects*; D018589:Gastroparesis / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology; D054439:Ghrelin; D006801:Humans; D008297:Male; D008875:Middle Aged; D036361:Peptide Hormones / Q000097:blood / Q000627:therapeutic use*; D013270:Stomach / Q000000981:diagnostic imaging; D014463:Ultrasonography
D054439:Ghrelin; D036361:Peptide Hormones