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Disruption of the Pulsatile and Entropic Modes of Insulin Release during an Unvarying Glucose Stimulus in Elderly Individuals¹

Division of Geriatric Medicine, Department of Medicine, University of British Columbia (G.S.M.), Vancouver, British Columbia, Canada V6T 2B5; the Department of Medicine, University of Virginia (J.D.V.), Charlottesville, Virginia 22908; and the Department of Medicine, Massachusetts General Hospital Harvard Medical School (D.E.), Boston, Massachusetts 02114

Address all correspondence and requests for reprints (until June 30, 1999) to: Dr. Graydon Meneilly, 215 Hawken Drive, St. Lucia, Queensland 4067, Australia. E-mail: gmeneillly{at}uq.net.au After June 30, 1999:

Insulin is secreted in a pulsatile fashion with measurable orderliness (low entropy). Aging is characterized by alterations in pulsatile insulin release in the fasting state. We undertook the current studies to determine whether disruptions in pulsatile insulin release in response to sustained glucose infusion also accompany the age-related changes in carbohydrate metabolism. Healthy young (n = 10; body mass index, 23 ± 1 kg/m²; age, 23 ± 1 yr) and old (n = 10; body mass index, 24 ± 1 kg/m²; age, 80 ± 2 yr) volunteers underwent a 600-min hyperglycemic glucose clamp. During the entire 600 min, insulin was sampled every 10 min, and insulin release was evaluated by Cluster analysis. From 240–360 min, insulin was sampled every 1 min, and secretory pulse analysis was conducted using a multiparameter deconvolution technique. During the 1-min sampling interval, basal insulin secretion (P < 0.01), insulin production rate (P < 0.01), pulsatile mean and integrated insulin concentration (P < 0.01), insulin secretory burst mass (P < 0.01), and burst amplitude (P < 0.05) were reduced in the elderly. In addition, interpulse interval was increased in the aged (P < 0.05). In the 600-min studies, interpulse interval was greater in the aged (P < 0.01) and burst number (P < 0.01), basal concentration (P < 0.01), and burst increment (P < 0.05) were less. Approximate entropy, a measure of irregularity of insulin release, was increased in the aged, signifying the loss of orderliness of insulin secretion (P < 0.05).

We conclude that in response to a sustained (10-h) glucose infusion, normal aging is characterized by a reduction in mass and amplitude of rapid insulin pulses and a decrease in the frequency, amplitude, and regularity of ultradian pulses. Whether these changes in insulin pulsatility contribute directly to the age-related changes in carbohydrate metabolism will require further clinical studies.

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