levosulpiride and Diabetes-Mellitus--Type-1

Topics: Adult; Blood Glucose; Breath Tests; Cisapride; Cross-Over Studies; Diabetes Mellitus, Type 1; Female; Gastric Emptying; Gastrointestinal Agents; Gastroparesis; Humans; Hyperglycemia; Kinetics; Male; Middle Aged; Receptors, Dopamine D2; Sulpiride

We evaluated the effect of chronic administration of levosulpiride, a prokinetic drug that is a selective antagonist for D2 dopamine receptors, on the glycemic control of IDDM subjects.. The study was performed on 40 long-standing IDDM subjects with clinical signs of autonomic neuropathy and delayed gastric emptying. Gastric emptying time and glycemic parameters (diurnal glycemic profile and HbA1c) were checked under double-blind conditions before and after the administration of levosulpiride at the dosage of 25 mg t.i.d. orally for 6 months, or placebo.. No significant differences were noted in the glycemic and HbA1c values before and after 6 months of placebo administration. In contrast, after 6 months of levosulpiride, glycemic control had improved (HbA1c 6.7 +/- 0.4 and 5.7 +/- 0.3%, P < 0.01; mean daily glycemia 10.9 +/- 0.8 and 8.8 +/- 0.4 mmol/l, P < 0.05, at the start and at the end of the study), while the dosage of injected insulin (0.65 +/- 0.02 IU.kg-1.day-1) and the number of severe hypoglycemic episodes remained unchanged. After 6 months of levosulpiride therapy, the time of gastric emptying was significantly reduced from 321 +/- 14 to 261 +/- 9 min (P < 0.001) and dyspeptic symptoms had improved.. Our results show the importance of gastric emptying in the maintenance of glycemic control and the usefulness of chronic administration of levosulpiride in diabetic subjects with gastroparesis.

Topics: Administration, Oral; Adult; Autonomic Nervous System Diseases; Blood Glucose; Diabetes Mellitus, Type 1; Diabetic Neuropathies; Dopamine Antagonists; Double-Blind Method; Female; Gastric Emptying; Gastroparesis; Glycated Hemoglobin; Humans; Male; Middle Aged; Sulpiride; Time Factors

Antidopaminergic drugs may be useful in diabetic gastroparesis because the inhibitory activity of hyperglycemia on gastric motility seems to be related to dopamine receptor stimulation. For this reason, we evaluated the effect of levosulpiride on gastric emptying, dyspeptic symptoms, and metabolic parameters of insulin-treated diabetic patients.. Under double-blind conditions, 40 longstanding, insulin-treated dyspeptic patients with autonomic neuropathy and delayed gastric emptying were randomly submitted, with an interval of 15 days, to 4 wk of administration of both levosulpiride 25 mg t.i.d. and placebo according to a cross-over design. At the beginning of the study and after levosulpiride or placebo treatment, the gastric emptying time of a standard meal was measured ultrasonically; gastrointestinal symptom scores and glycaemic control were also evaluated.. Levosulpiride reduced significantly (p < 0.001) the gastric emptying time from 416 +/- 58 to 322 +/- 63 min, whereas placebo did not change it consistently (396 +/- 58 vs 372 +/- 72 min). Symptoms improved significantly (p < 0.001) with levosulpiride compared with placebo. However, there was no significant correlation between the acceleration of gastric emptying and the symptomatological improvement. The reduction of mean plasma glycosylated hemoglobin concentrations after levosulpiride (7.3 +/- 1.9 vs 5.8 +/- 1.3) was not significantly different (p = not significant) compared with placebo (6.8 +/- .7 vs 6.1 +/- 1.4).. Our study first demonstrates that levosulpiride has an accelerating effect on the emptying of solids from the stomach of patients with diabetic gastroparesis. The drug is also effective in relieving upper gastrointestinal symptoms in patients whose gastric emptying times remain very slow. Our findings suggest, but do not prove, that better blood glucose control could be achieved with reduction of gastric emptying time; further trials are needed in this field.

Topics: Cross-Over Studies; Diabetes Mellitus, Type 1; Dopamine Antagonists; Double-Blind Method; Dyspepsia; Female; Gastric Emptying; Gastrointestinal Agents; Gastroparesis; Glycated Hemoglobin; Humans; Male; Middle Aged; Sulpiride; Time Factors