Induced-Hyperglycemia Attenuates Erythromycin-Induced Acceleration of Hypertonic Liquid-Phase Gastric Emptying in Type-I Diabetic Patients

Abstract

Background: Erythromycin has been found to be a gastrointestinal prokinetic agent of hypertonic liquids, while acute hyperglycemia has been associated with delayed gastric emptying in diabetic patients. Aim: To investigate whether hyperglycemia, per se, reduces gastric motility during erythromycin-induced acceleration on gastric emptying of hypertonic liquids in diabetic patients. Methods: In 12 type-I diabetic patients following a hypertonic radiolabeled liquid meal, gastric emptying was measured scintigraphically during normoglycemia (5–8.9 mmol/l glucose) or hyperglycemia induced by intravenous (16–19 mmol/l) glucose infusion. The tests were performed on 4 separate days in random order after administering either placebo or 200 mg i.v. erythromycin. Results: In the hyperglycemic state compared to normoglycemia, the gastric emptying of the hypertonic liquid was reduced after placebo or erythromycin administration. The lag-phase duration (17.8±5.5 and 7.8±4.5 vs. 10.8±3.4 and 3.7±2.5 min, respectively, p<0.001), the overall gastric emptying time of the half meal (52.8±13 and 24.9±5.5 vs. 42.5±10.5 min and 16.6±6 min, respectively, p<0.001) and the retained percentage of liquid meal in the stomach at 60 and 100 min postprandially (p<0.001) were significantly increased. Conclusions: The erythromycin-induced acceleration on gastric emptying of hypertonic liquids in diabetic patients is related to the plasma glucose level. The induced hyperglycemia reduces the erythromycin-induced acceleration of liquid-phase gastric emptying, decreasing the overall gastric emptying rate. In spite of the inhibitory effect of induced hyperglycemia on the gastric emptying of hypertonic liquids, erythromycin is still able to accelerate the emptying rate and could prove to be a useful prokinetic agent under hyperglycemic conditions.

Effect of itopride on gastric emptying in longstanding diabetes mellitus

“…Marked hyperglycaemia (blood glucose 16–20 mmol L −1 ) 34 and even blood glucose concentrations that are within the normal postprandial range (4–8 mmol L −1 ), 35 slow GE when compared with euglycaemia, while insulin‐induced hypoglycaemia accelerates emptying 36 . Acute hyperglycaemia, including changes in the blood glucose concentration within the postprandial range, may also attenuate the response to prokinetic drugs 10,12–14 . Hence, while we ensured that the blood glucose concentration immediately prior to the GE measurement was <12 mmol L −1 and the mean blood glucose during the GE measurements were <10 mmol L −1 , we cannot discount the possibility that the effects of itopride on GE may be more marked during euglycaemia.…”

“…9 The prokinetic effect of some drugs, including erythromycin and cisapride, is also attenuated during hyperglycaemia. [10][11][12][13][14] Hence, current pharmacological therapy is suboptimal and there is a need for new options.…”

Nutrition concerns for the patient with gastroparesis

“…Hyperglycemia can also attenuate the motor-stimulatory effects of erythromycin [11,12]. A more extensive review of nutritional assessment in patients with gastroparesis is available elsewhere [13••].…”

Current Concepts in Gastric Motility in Diabetes Mellitus

“…When given orally, erythromycin has greater efficacy as a suspension than as a tablet [233], but is less effective than the intravenous way [231]. However, hyperglycaemia attenuates the gastrokinetic effect of erythromycin [234][235][236]. Side effects such as nausea, bloating, abdominal cramps, diarrhoea, rash and allergic manifestations limit the use of erythromycin, at least for long-time treatment [237], but are dose-related.…”