Physiological responses during hypoglycaemia induced by regular human insulin or a novel human analogue, insulin glargine.
OBJECTIVE
Glargine, a product of recombinant technology, has different structural and physicochemical properties compared with native human insulin. We determined whether such differences are associated with alterations in the responses to hypoglycaemia induced by glargine.


METHODS
Nineteen adults (six healthy and 13 with type 1 diabetes) underwent a 5-h hyperinsulinaemic (2 mU/kg/min(-1)) stepped hypoglycaemic clamps (hourly targets of 4.7, 4.2, 3.6, 3.1 and 2.5 mmol/l, respectively) on two occasions using intravenous infusion of regular human insulin or glargine, in random sequence. Hypoglycaemic symptoms, counter-regulatory hormones and glucose disposal rates were assessed at intervals throughout the clamps. A 1-week 'wash out' period was observed between studies.


RESULTS
The peak total symptoms scores (mean +/- s.e.m.) at nadir blood glucose (2.5 mmol/1) were 18.83 +/- 2.68 (healthy) and 17.46 +/- 3.62 (diabetic) during regular insulin, and 18.50 +/- 3.20 (healthy) and 19.08 +/- 3.83 (diabetic) during glargine infusion. The peak epinephrine levels during hypoglycaemia were 767.8 +/- 140.4 pg/ml (regular insulin) and 608.8 +/- 129.9 pg/ml (glargine) among healthy subjects, and 332.5 +/- 54.8 pg/ml (regular insulin) and 321.8 +/- 67.4 pg/ml (glargine) in diabetic patients. Diabetic patients had blunted glucagon responses during hypoglycaemia with either insulin. Both insulins also elicited similar rates of glucose disposal.


CONCLUSIONS
We conclude that insulin glargine and regular human insulin elicit comparable symptomatic and counter-regulatory hormonal responses during hypoglycaemia in healthy or diabetic subjects, and induce similar rates of glucose disposal. Since glargine is designed for subcutaneous (s.c.) use, it is possible (though unlikely) that our findings obtained using an intravenous protocol could differ from responses to hypoglycaemia induced by the s.c. route.
Department of Medicine, University of Mississippi Medical Center, Jackson 39216, USA. sdagogojack@medicine.umsmed.edu
S
S
Dagogo-Jack
H
H
Askari
B
B
Morrill
L L
LL
Lehner
B
B
Kim
X
X
Sha
D000328:Adult; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism*; D001794:Blood Pressure / Q000187:drug effects; D002096:C-Peptide / Q000097:blood; D018592:Cross-Over Studies; D003922:Diabetes Mellitus, Type 1 / Q000097:blood*; D004311:Double-Blind Method; D004837:Epinephrine / Q000097:blood; D005260:Female; D005934:Glucagon / Q000097:blood; D015309:Glucose Clamp Technique; D006339:Heart Rate / Q000187:drug effects; D019382:Human Growth Hormone / Q000097:blood; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D006946:Hyperinsulinism; D007003:Hypoglycemia / Q000097:blood / Q000139:chemically induced / Q000503:physiopathology*; D007328:Insulin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood* / Q000494:pharmacology*; D000069036:Insulin Glargine; D049528:Insulin, Long-Acting; D008297:Male; D009638:Norepinephrine / Q000097:blood; D011994:Recombinant Proteins / Q000494:pharmacology; D012016:Reference Values
D001786:Blood Glucose; D002096:C-Peptide; D007328:Insulin; D049528:Insulin, Long-Acting; D011994:Recombinant Proteins; D019382:Human Growth Hormone; D000069036:Insulin Glargine; D005934:Glucagon; D006854:Hydrocortisone; D009638:Norepinephrine; D004837:Epinephrine