Insulin responses to glucose and isoproterenol decrease with age.

Abstract

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.