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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.

AbstractOBJECTIVE:
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.
AuthorsFilip K Knop, Tina Vilsbøll, Steen Larsen, Sten Madsbad, Jens J Holst, Thure Krarup
JournalDiabetes care (Diabetes Care) Vol. 26 Issue 9 Pg. 2581-7 (Sep 2003) ISSN: 0149-5992 [Print] United States
PMID12941722 (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)

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