Effect of antecedent glucose control on cerebral function during hypoglycemia.
OBJECTIVE
The incidence of both severe and asymptomatic hypoglycemia is increased threefold in intensively treated diabetic patients. To examine whether this reflects cerebral adaptation to low blood glucose levels, we investigated the effect of preceding glycemic experience on hormonal, EEG, and evoked potential responses to experimentally induced hypoglycemia with the slow-fall clamp.


METHODS
Three groups were examined: well-controlled diabetic patients and patients with insulinoma (group 1), poorly controlled diabetic patients (group 2), and nondiabetic subjects (group 3).


RESULTS
The glucose threshold for epinephrine release was lower in group 1 (2.3 +/- 0.1 vs. 3.0 +/- 0.3 and 3.1 +/- 0.1 mM, P less than 0.02), and the peak epinephrine response was reduced (1.29 +/- 0.36 vs. 5.48 +/- 1 and 5.62 +/- 1.2 nM, P less than 0.01) compared with groups 2 and 3, whereas symptoms were not perceived until a lower blood glucose level had been reached (2.0 +/- 0.2 vs. 3.3 +/- 0.4 and 2.6 +/- 0.2 mM, P less than 0.01). Other counterregulatory responses were similarly delayed and diminished. In contrast, EEG changes that were compatible with hypoglycemia were detected in all subjects in group 1 (blood glucose 1.9 +/- 0.1 mM) but in only two in group 2 and none in group 3, despite similar blood glucose nadirs.


CONCLUSIONS
The glycemic threshold for hormonal responses to hypoglycemia falls in individuals with intensively treated diabetes or insulinomas, but these patients are more likely to develop EEG abnormalities during hypoglycemia. This disparity helps explain the increased vulnerability of intensively treated patients to severe hypoglycemia.
Amiel
S A
SA
Department of Diabetes and Immunogenetics, Medical College of St. Bartholomew's Hospital, London, England, United Kingdom.
Pottinger
R C
RC
Archibald
H R
HR
Chusney
G
G
Cunnah
D T
DT
Prior
P F
PF
Gale
E A
EA
D000328:Adult; D001786:Blood Glucose / Q000378:metabolism*; D001794:Blood Pressure; D001921:Brain / Q000503:physiopathology*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology*; D004558:Electric Stimulation; D004569:Electroencephalography; D004837:Epinephrine / Q000097:blood; D005073:Evoked Potentials, Somatosensory; D005260:Female; D015309:Glucose Clamp Technique; D013006:Growth Hormone / Q000097:blood; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007003:Hypoglycemia / Q000097:blood / Q000503:physiopathology*; D008297:Male; D008475:Median Nerve / Q000503:physiopathology; D009638:Norepinephrine / Q000097:blood; D011187:Posture; D014636:Valsalva Maneuver
D001786:Blood Glucose; D013006:Growth Hormone; D006854:Hydrocortisone; D009638:Norepinephrine; D004837:Epinephrine