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 (fivemen, 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 control led by euglycaemic clamp. Gastric emptying rate (GER) was calculated by real tim e ultrasound following a test meal. Blood was sampled for ghrelin, growth hormon e (GH), and pancreatic polypeptide (PP) levels. Cardiovagal neuropathy was asses sed using the Mayo Clinic composite autonomic severity score (range 0 (normal)- 3). Results: Baseline ghrelin levels were mean 445 (SEM 36) pmol/l. Ghrelin infu sion achieved a peak plasma level of 2786 (188) pmol/l at 90 minutes, correspond ing to a peak GH of 70.9 (19.8) pmol/l. Ghrelin increased gastric emptying in se ven of 10 patients (30 (6)%to 43 (5)%; p = 0.04). Impaired cardiovagal tone co rrelated inversely with peak postprandial PP values (p < 0.05) but did not corre late with GER. Conclusions: Ghrelin increases gastric emptying in patients with diabetic gastroparesis. This is independent of vagal tone. We propose that analo gues of ghrelin may represent a new class of prokinetic agents.
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