Glucagon-like peptide I improved glycemic control in type I diabetes

被引：56

作者：

Margaret T Behme

John Dupré

Thomas J McDonald

机构：

[1] Department of Medicine, University of Western Ontario, London Health Sciences Centre, London

来源：

BMC Endocrine Disorders | / 3卷 / 1期

关键词：

Glycemic Control; Gastric Emptying; Intensive Insulin Therapy; Pancreatic Polypeptide; Continuous Subcutaneous Insulin Infusion;

D O I：

10.1186/1472-6823-3-3

中图分类号：

学科分类号：

摘要：

Background: Glucagon-like peptide-1 (GLP-1) and its agonists are under assessment in treatment of type 2 diabetes, by virtue of their antidiabetic actions, which include stimulation of insulin secretion, inhibition of glucagon release, and delay of gastric emptying. We examined the potential of GLP-1 to improve glycemic control in type 1 diabetes with no endogenous insulin secretion. Methods: Dose-finding studies were carried out to establish mid range doses for delay of gastric emptying indicated by postponement of pancreatic polypeptide responses after meals. The selected dose of 0.63 micrograms/kg GLP-1 was administered before breakfast and lunch in 8-hour studies in hospital to establish the efficacy and safety of GLP-1. In outside-hospital studies, GLP-1 or vehicle was self-administered double-blind before meals with usual insulin for five consecutive days by five males and three females with well-controlled C-peptide-negative type 1 diabetes. Capillary blood glucose values were self-monitored before meals, at 30 and 60 min after breakfast and supper, and at bedtime. Breakfast tests with GLP-1 were conducted on the day before and on the day after 5-day studies. Paired t-tests and ANOVA were used for statistical analysis. Results: In 8-hour studies time-averaged incremental (delta) areas under the curves(AUC) for plasma glucose through 8 hours were decreased by GLP-1 compared to vehicle (3.2 ± 0.9, mean ± se, vs 5.4 ± 0.8 mmol/l, p < .05), and for pancreatic polypeptide, an indicator of gastric emptying, through 30 min after meals (4.0 ± 3.1 vs 37 ± 9.6 pmol/l, p < .05) with no adverse effects. Incremental glucagon levels through 60 min after meals were depressed by GLP-1 compared to vehicle (-3.7 ± 2.5 vs 3.1 ± 1.9 ng/l, p < .04). In 5-day studies, AUC for capillary blood glucose levels were lower with GLP-1 than with vehicle (-0.64 ± 0.33 vs 0.34 ± 0.26 mmol/l, p < .05). No assisted episode of hypoglycaemia or change in insulin dosage occurred. Breakfast tests on the days immediately before and after 5-day trials showed no change in the effects of GLP-1. Conclusion: We have demonstrated that subcutaneous GLP-1 can improve glucose control in type 1 diabetes without adverse effects when self-administered before meals with usual insulin during established intensive insulin treatment programs. © 2003 Behme et al; licensee BioMed Central Ltd.

引用

共 13 条

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[12] Dupre J., Behme M.T., McDonald T.J., Exendin-4 reduces glucose excursions after meals in insulin-treated diabetes, Abstract Diabetes, 51, SUPPL. 2, (2002)
[13] Juhl C.B., Hollingdal M., Sturis J., Jakobsen G., Agerso H., Veldhuis J., Porksen N., Schmitz O., Bedtime administration of NN2211 a long-acting GLP-1 derivative, substantially reduces fasting and postprandial glycemia in type 2 diabetes, Diabetes, 51, pp. 424-429, (2002)

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