Altered hierarchy of protective responses against severe hypoglycemia in normal aging in healthy men.
OBJECTIVE
To investigate the effect of normal aging on the protective responses against hypoglycemia, in view of the fact that type II diabetes is primarily a disease of aging, and its treatment is associated with risk of hypoglycemia with cognitive impairment.


METHODS
Plasma glucose was lowered stepwise from 5 to 2.4 mmol/l and restored by manipulation of an infusion of 20% glucose during 220-min intravenous infusion of 1.5 mU.kg-1.min-1 soluble insulin in 14 men; 7 were aged 60-70 years and the other 7 were 22-26 years. Changes in neurohumoral responses, subjective awareness, and choice reaction time were assessed.


RESULTS
Hormonal responses were similar in the two groups, but symptoms began earlier in the younger men (at a plasma glucose of 3.6 +/- 0.1 vs. 3.0 +/- 0.2 mmol/l, P = 0.02) and were more intense (P = 0.03). Four-choice reaction time, a measure of psychomotor coordination, deteriorated earlier in the older men (at a plasma glucose of 3.0 +/- 0.1 vs. 2.6 +/- 0.1 mmol/l, P = 0.07) and to a greater degree. The difference between the glucose level for subjective awareness of hypoglycemia and the onset of cognitive dysfunction was lost in the older men (0.0 +/- 0.2 vs. 0.8 +/- 0.1 mmol/l, P < 0.007).


CONCLUSIONS
Older men are prone to more severe cognitive impairment during hypoglycemia than younger men and are less likely to experience prior warning symptoms if blood glucose falls. This effect of normal aging may contribute to the risk of severe hypoglycemia in older diabetic patients treated with sulfonylureas and insulin.
Matyka
K
K
Department of Medicine, King's College School of Medicine and Dentistry, London, U.K.
Evans
M
M
Lomas
J
J
Cranston
I
I
Macdonald
I
I
Amiel
S A
SA
D000328:Adult; D000368:Aged; D000375:Aging / Q000097:blood / Q000502:physiology* / Q000523:psychology; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D001794:Blood Pressure; D002096:C-Peptide / Q000097:blood; D003071:Cognition / Q000502:physiology*; D015331:Cohort Studies; D004837:Epinephrine / Q000097:blood / Q000378:metabolism; D005934:Glucagon / Q000097:blood; D015309:Glucose Clamp Technique; D006339:Heart Rate; D019382:Human Growth Hormone / Q000097:blood; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007003:Hypoglycemia / Q000097:blood / Q000139:chemically induced / Q000503:physiopathology* / Q000523:psychology; D007328:Insulin / Q000097:blood; D008297:Male; D008875:Middle Aged; D011597:Psychomotor Performance / Q000187:drug effects / Q000502:physiology*
D001786:Blood Glucose; D002096:C-Peptide; D007328:Insulin; D019382:Human Growth Hormone; D005934:Glucagon; D006854:Hydrocortisone; D004837:Epinephrine