Abstract | OBJECTIVE:
Glucagon-like peptide 1 (GLP-1) is a proglucagon derivative secreted primarily from the L-cells of the small intestinal mucosa in response to the ingestion of meals. GLP-1 stimulates insulin secretion and inhibits glucagon secretion. It has previously been shown that intravenous or subcutaneous administration of GLP-1 concomitant with intravenous glucose results in hypoglycemia in healthy subjects. Because GLP-1 is also effective in type 2 diabetic patients and is currently being evaluated as a therapeutic agent, it is important to investigate whether GLP-1 may cause hypoglycemia in such patients. We have previously shown that GLP-1 does not cause hypoglycemia in obese type 2 diabetic patients with insulin resistance amounting to 5.4 +/- 1.1 according to homeostasis model assessment (HOMA). In this study, we investigated diabetic patients with normal or close to normal insulin sensitivity. RESEARCH DESIGN AND METHODS: Eight lean type 2 diabetic patients (group 1) aged 60 years (range 50-72) with BMI 23.1 kg/m(2) (20.3-25.5) and HbA(1c) 8.0% (6.9-11.4) and eight patients with type 2 diabetes secondary to chronic pancreatitis (group 2) aged 52 years (41-62) with BMI 21.9 kg/m(2) (17.6-27.3) and HbA(1c) 7.8% (6.2-12.4) were given a subcutaneous injection of 1.5 nmol GLP-1/kg body wt. Then, 15 min later, at the time of peak GLP-1 concentration, plasma glucose (PG) was raised to 15 mmol/l with an intravenous glucose bolus. HOMA (mean +/- SEM) showed insulin resistance amounting to 1.9 +/- 0.3 and 1.7 +/- 0.5 in the two groups, respectively. RESULTS: In both groups, PG decreased rapidly and stabilized at 7.5 mmol/l (range 3.9-10.1) and 7.2 mmol/l (3.1-10.9) in groups 1 and 2, respectively, after 90 min. Neither symptoms of hypoglycemia nor biochemical hypoglycemia were observed in any patient. CONCLUSIONS: We conclude that a GLP-1-based therapy would not be expected to be associated with an increased risk of hypoglycemia in insulin-sensitive type 2 diabetic patients.
|
Authors | Filip K Knop, Tina Vilsbøll, Steen Larsen, Sten Madsbad, Jens J Holst, Thure Krarup |
Journal | Diabetes care
(Diabetes Care)
Vol. 26
Issue 9
Pg. 2581-7
(Sep 2003)
ISSN: 0149-5992 [Print] United States |
PMID | 12941722
(Publication Type: Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)
|
Chemical References |
- Blood Glucose
- C-Peptide
- Glycated Hemoglobin A
- Insulin
- Peptide Fragments
- Protein Precursors
- Glucagon-Like Peptide 1
- Glucagon
|
Topics |
- Adult
- Aged
- Blood Glucose
(drug effects, metabolism)
- C-Peptide
(blood)
- Chronic Disease
- Diabetes Mellitus
(drug therapy, etiology)
- Diabetes Mellitus, Type 2
(drug therapy)
- Glucagon
(administration & dosage, blood, therapeutic use)
- Glucagon-Like Peptide 1
- Glycated Hemoglobin
(analysis)
- Humans
- Hypoglycemia
(epidemiology)
- Injections, Subcutaneous
- Insulin
(blood)
- Kinetics
- Middle Aged
- Pancreatitis
(complications)
- Peptide Fragments
(administration & dosage, blood, therapeutic use)
- Protein Precursors
(administration & dosage, blood, therapeutic use)
|