The stimulation of antral motility by erythromycin is attenuated by hyperglycemia

OBJECTIVE: Diabetic gastroparesis is usually treated with prokinetic drugs, of which the most potent, when given intravenously during euglycemia, is e rythromycin. Recent studies have demonstrated that the gastrokinetic effect s of erythromycin are attenuated by hyperglycemia. The aim of this study wa s to determine whether the effects of erythromycin on antropyloroduodenal m otility, including the organization of antral pressure waves, are modified by hyperglycemia. METHODS: A total of eight healthy male volunteers (median age 24 yr) were s tudied on 2 days each in randomized order. A manometric assembly, incorpora ting six antral, two pyloric, and seven duodenal sideholes and a pyloric sl eeve sensor, was positioned with the sleeve spanning the pylorus. The blood glucose concentration was stabilized at about 5 mmol/L (euglycemia) or 15 mmol/L (hyperglycemia). After 30 min (T = 0), an intraduodenal lipid infusi on (1.5 kcal/min) was commenced and continued until the end of the study. A t T = 20 minutes, erythromycin (200 mg) as the lactobionate was infused int ravenously over 20 min, followed by 100 mg over the next 40 min. RESULTS: Intravenous erythromycin increased the amplitude of antral waves d uring intraduodenal lipid infusion at both blood glucose concentrations (p < 0.01 for euglycemia and p < 0.05 for hyperglycemia). After erythromycin ( T = 20 to T = 80), the frequency (p < 0.05) and amplitude (p < 0.01) of ant ral waves were less during hyperglycemia than euglycemia. Both propagated ( p < 0.0005) and nonpropagated (p < 0.01) antral waves were decreased by hyp erglycemia, but the suppression of propagated waves was greater (p < 0.05). Erythromycin reduced the frequency (p = 0.09) but increased the amplitude (p < 0.05) of phasic pyloric pressures, and decreased basal pyloric pressur e (p < 0.0005). The frequency (p = 0.06) and amplitude (p < 0.05) of phasic pyloric waves during erythromycin infusion were slightly less during hyper glycemia than euglycemia, whereas there was no effect of the blood glucose concentration on basal pyloric pressure. Erythromycin increased the amplitu de (p < 0.001) but not the frequency of duodenal waves; the frequency and a mplitude of duodenal waves did not differ between the two blood glucose con centrations. CONCLUSIONS: Hyperglycemia attenuates the stimulation of antral pressures a nd propagated antral sequences by erythromycin, but not the effects of eryt hromycin on pyloric or duodenal motility. (Am J Gastroenterol 2000;95:2233- 2241. (C) 2000 by Am. Cell. of Gastroenterology).