The role of endocrine counterregulation for estimating insulin sensitivity from intravenous glucose tolerance tests.
BACKGROUND
During insulin-modified frequently sampled iv glucose tolerance tests (IM-FSIGT), which allow assessment of insulin action, plasma glucose can markedly decrease.


OBJECTIVE
This study aimed to assess the counterregulatory impact of the insulin-induced fall of glucose on minimal model-derived indices of insulin sensitivity (S(I)) and glucose effectiveness.


METHODS
Thirteen nondiabetic volunteers (seven males, six females, aged 26 +/- 1 yr, body mass index 22.1 +/- 0.7 kg/m(2)) were studied.


METHODS
All participants were studied in random order during IM-FSIGT (0.3 g/kg glucose; 0.03 U/kg insulin at 20 min) and during identical conditions but with a variable glucose infusion preventing a decrease of plasma glucose concentration below euglycemia (IM-FSIGT-CLAMP). Five participants additionally underwent euglycemic-hyperinsulinemic (1 mU.kg(-1).min(-1)) clamp tests.


RESULTS
Plasma glucose declined during IM-FSIGT to its nadir of 50 +/- 3 mg/dl at 60 min in parallel to a rise (P < 0.05 vs. basal) of plasma glucagon, cortisol, epinephrine, and GH. Glucose infusion rates of 4.6 +/- 0.5 mg.kg(-1).min(-1) between 30 and 180 min during IM-FSIGT-CLAMP prevented the decline of plasma glucose and the hypoglycemia counterregulatory hormone response. S(I) was approximately 68% lower during IM-FSIGT (3.40 +/- 0.36 vs. IM-FSIGT-CLAMP: 10.71 +/- 1.06 10(-4).min(-1) per microU/ml, P < 0.0001), whereas glucose effectiveness did not differ between both protocols (0.024 +/- 0.002 vs. 0.021 +/- 0.003 min(-1), P = NS). Compared with the euglycemic hyperinsulinemic clamp test, S(I) expressed in identical units from IM-FSIGT was approximately 66% (P < 0.001) lower but did not differ between the euglycemic hyperinsulinemic clamp test and the IM-FSIGT-CLAMP (P = NS).


CONCLUSIONS
The transient fall of plasma glucose during IM-FSIGT results in lower estimates of S(I), which can be explained by hormonal response to hypoglycemia.
Brehm
Attila
A
Division of Endocrinology and Metabolism, Department of Internal Medicine 3, Medical University of Vienna, Währinger Gürtel 18-20, A-1090 Vienna, Austria.
Thomaseth
Karl
K
Bernroider
Elisabeth
E
Nowotny
Peter
P
Waldhäusl
Werner
W
Pacini
Giovanni
G
Roden
Michael
M
D000328:Adult; D001786:Blood Glucose / Q000032:analysis*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D005934:Glucagon / Q000097:blood; D015309:Glucose Clamp Technique; D005951:Glucose Tolerance Test; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007328:Insulin / Q000097:blood / Q000494:pharmacology*; D008297:Male; D009638:Norepinephrine / Q000097:blood
D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D005934:Glucagon; D006854:Hydrocortisone; D009638:Norepinephrine