Insulin responses to glucose and isoproterenol decrease with age.
BACKGROUND
Older trauma patients are less tolerant of glucose loads than are young patients, in part as a result of diminished insulin response. We hypothesized that diminished insulin responses result from reduced pancreatic sensitivity to beta-adrenergic stimulation.


METHODS
We studied healthy subjects prospectively at a clinical investigation unit, to compare young (n = 6, mean age 21 [standard deviation {SD} 2] yr) and older people (n = 6, mean 63 [SD 2] yr). Paired studies of isoproterenol infusion, alone and in conjunction with a 2-hour hyperglycemic glucose clamp, were conducted in each subject. Heart rate, serum insulin concentration and other hemodynamic, biochemical, and physiologic variables were measured.


RESULTS
Heart rate increased less markedly in response to isoproterenol in older than in young subjects (p < 0.01). Serum insulin during infusion accompanied by hyperglycemic clamp was also lower (467 [SD 135] pmol/L in older v. 755 [SD 284] pmol/L in young subjects, p < 0.05), despite similar hyperglycemia. Whole-body disposal of exogenous glucose was lower in older (5.8 [SD 1.7] mg/kg/min) than in young subjects (9.6 [SD 3.9], p < 0.05).


CONCLUSIONS
Heart rate and serum insulin responses to combined isoproterenol infusion and glucose loading were both lower in healthy older subjects than in the young. Diminished tissue sensitivity to beta-adrenergic signals may contribute to the impaired insulin response and exaggerated glucose intolerance displayed by older patients after injury and during acute illness.
Watters
James M
JM
Department of Surgery, University of Ottawa, and Ottawa Health Research Institute, Ottawa Hospital, Ottawa, Ont. jwatters@ohri.ca
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000328:Adult; D000375:Aging / Q000502:physiology*; D005260:Female; D005947:Glucose / Q000494:pharmacology; D015309:Glucose Clamp Technique; D018149:Glucose Intolerance / Q000503:physiopathology; D006339:Heart Rate / Q000502:physiology; D006801:Humans; D007328:Insulin / Q000097:blood*; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D010179:Pancreas / Q000503:physiopathology*; D011446:Prospective Studies; D011659:Pulmonary Gas Exchange / Q000187:drug effects
D000318:Adrenergic beta-Agonists; D007328:Insulin; D005947:Glucose; D007545:Isoproterenol