Endocrine Abstracts

Background

Diabetic gastroparesis is a disabling condition with no consistently effective treatment. Ghrelin infusion, in animal studies, increases gastric emptying and reverses post-operative ileus. We present the results of the first 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 (5 pmol/kg/min) or saline on two separate occasions during euglycaemic clamp. Subjective symptoms were assessed using visual analogue scales (VAS). Gastric emptying rate (GER) was calculated by ultrasound following a test meal. Blood was sampled throughout for ghrelin, growth hormone (GH) and pancreatic polypeptide (PP) levels. Cardiovagal neuropathy was assessed by ECG using the Mayo CASS scale [range 0(normal)-3].

Results

Baseline ghrelin levels were 440±43 pmol/l (mean±SEM) with no significant differences between each study day. Ghrelin infusion achieved a peak plasma level of 2773±238 pmol/l at 90 minutes, corresponding with a peak GH of 70.9±19 pmol/l (baseline GH<0.5 pmol/l), confirming biologically effective doses of ghrelin had been infused. By ultrasound criteria 8 out of 10 of the subjects had delayed gastric emptying and in 7 of these 8, ghrelin infusion increased GER (43±6% vs 30±5%, ghrelin vs saline respectively, mean±SEM, p=0.04). Ghrelin did not increase gastric emptying in the 2 subjects with normal baseline GER. There were no significant differences between infusions in VAS scores for any symptoms (p>0.05). Impaired cardiovagal tone correlated inversely with peak post-prandial PP values (p<0.05) but did not correlate with GER during ghrelin infusion.

Conclusions

Ghrelin increases gastric emptying in patients with diabetic gastroparesis. Increased gastric emptying is not associated with an acute improvement in symptoms and appears to be independent of vagal tone.