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.
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.


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.
Knop
Filip K
FK
Department of Internal Medicine F, Gentofte Hospital, Hellerup, Denmark. filipknop@dadlnet.dk
Vilsbøll
Tina
T
Larsen
Steen
S
Madsbad
Sten
S
Holst
Jens J
JJ
Krarup
Thure
T
D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D002096:C-Peptide / Q000097:blood; D002908:Chronic Disease; D003920:Diabetes Mellitus / Q000188:drug therapy* / Q000209:etiology; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D005934:Glucagon / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D052216:Glucagon-Like Peptide 1; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007003:Hypoglycemia / Q000453:epidemiology*; D007279:Injections, Subcutaneous; D007328:Insulin / Q000097:blood; D007700:Kinetics; D008875:Middle Aged; D010195:Pancreatitis / Q000150:complications*; D010446:Peptide Fragments / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D011498:Protein Precursors / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*
D001786:Blood Glucose; D002096:C-Peptide; D005934:Glucagon; D052216:Glucagon-Like Peptide 1; D006442:Glycated Hemoglobin; D007328:Insulin; D010446:Peptide Fragments; D011498:Protein Precursors