No Hypoglycemia After Subcutaneous Administration of Glucagon-Like Peptide-1 in Lean Type 2 Diabetic Patients and in Patients With Diabetes Secondary to Chronic Pancreatitis
- Filip K. Knop, MD1,
- Tina Vilsbøll, MD1,
- Steen Larsen, MD, DMSC2,
- Sten Madsbad, MD, DMSC3,
- Jens J. Holst, MD, DMSC4 and
- Thure Krarup, MD, DMSC1
- 1Department of Internal Medicine F, Gentofte Hospital, Hellerup, Denmark
- 2Department of Internal Medicine M, Glostrup Hospital, Glostrup, Denmark
- 3Department of Endocrinology, Hvidovre Hospital, Hvidovre, Denmark
- 4Department of Medical Physiology, the Panum Institute, University of Copenhagen, Copenhagen, Denmark
- Address correspondence and reprint requests to Filip Krag Knop, MD, Department of Internal Medicine F, Gentofte Hospital, University of Copenhagen, Niels Andersensvej 65, DK-2900 Hellerup, Denmark. E-mail: filipknop{at}dadlnet.dk
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/m2 (20.3–25.5) and HbA1c 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/m2 (17.6–27.3) and HbA1c 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.
- DPP-IV, dipeptidyl peptidase IV
- FPG, fasting plasma glucose
- GLP-1, glucagon-like peptide 1
- HOMA, homeostasis model assessment
- iAUC, incremental area under the curve
- PG, plasma glucose
- RIA, radioimmunoassay
- WHO, World Health Organization
Footnotes
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A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.
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- Accepted June 1, 2003.
- Received January 28, 2003.
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