Effects of dipeptide administration on hypoglycaemic counterregulation in type 1 diabetes.
OBJECTIVE
To investigate if a dipeptide made of glutamine and alanine is able to contribute to the recovery from insulin-induced hypoglycaemia in type 1 diabetes.


METHODS
Fifteen adult type 1 patients were randomly assigned to study group (n=7): intravenous infusion of 20 g Dipeptiven in normal saline (i.e., 8 g alanine and 13 g glutamine), or control group (n=8): same infusion, normal saline only. A 150 min gradual hypoglycaemic hyperinsulinemic clamp was administered after 2 h of infusion. Counterregularory hormones, symptoms, and cognitive function (4 choice reaction test) were regularly measured during the study.


RESULTS
Blood glucose and glucose infusion rates were similar in the 2 groups. Circulating levels of alanine and glutamine peaked at 90 min and remained elevated throughout the test. This was associated with significant differences in: glucagonemia 107 +/- 20 vs 58 +/- 8 pg/ml, and neuroglycopenic symptoms scores: 7 +/- 3 vs 18 +/- 13, at t 150 min, in study and control group, p<0.05. Dysautonomic symptoms, cognitive tests as well as epinephrine, norepinephrine, cortisol and growth hormone were similar between groups.


CONCLUSIONS
Intravenous infusion of a dipeptide made of alanine and glutamine is capable to reactivate glucagon secretion during insulin-induced hypoglycaemia and to reduce hypoglycaemic symptoms.
M'bemba
J
J
Inserm U341, Department of Diabetology, Hospital Assistance Publique, Paris, France.
Cynober
L
L
de Bandt
P
P
Taverna
M
M
Chevalier
A
A
Bardin
C
C
Slama
G
G
Selam
J L
JL
D000328:Adult; D017668:Age of Onset; D000596:Amino Acids / Q000378:metabolism; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism*; D003071:Cognition; D003922:Diabetes Mellitus, Type 1 / Q000097:blood*; D004151:Dipeptides / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D005934:Glucagon / Q000097:blood* / Q000187:drug effects / Q000378:metabolism; D015309:Glucose Clamp Technique; D006706:Homeostasis; D006801:Humans; D007003:Hypoglycemia / Q000097:blood*; D007262:Infusions, Intravenous; D007328:Insulin / Q000097:blood / Q000378:metabolism; D000078790:Insulin Secretion; D008297:Male; D010465:Perception; D012016:Reference Values
D000596:Amino Acids; D001786:Blood Glucose; D004151:Dipeptides; D007328:Insulin; D005934:Glucagon; C054122:alanylglutamine